US 201401 13826A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0113826A1 Fallon et al. (43) Pub. Date: Apr. 24, 2014

(54) POLYSACCHARIDE ESTERMICROSPHERES A24D3/14 (2006.01) AND METHODS AND ARTICLES RELATING A618/02 (2006.01) THERETO (52) U.S. Cl. (71) Applicant: Celanese Acetate LLC, Irving, TX (US) CPC ...... A2.3L I/22016 (2013.01); A61K 8/025 (2013.01); A0IN 25/34 (2013.01); A24D 3/14 (72) Inventors: Denis G. Fallon, Blacksburg, VA (US); (2013.01) Thomas S. Garrett, Narrows, VA (US); USPC 504/358; 424/401; 424/405; 424/64; 424/69; Lawton E. Kizer, Blacksburg, VA (US); 424/63; 424/70.7; 13 1/332: 426/650: 426/648 Karen L. Zazzara, Blacksburg, VA (US); Michael T. Combs, Shady Spring, WV (US); Richard K. Johnson, Blacksburg, VA (US); Gary Dehart, (57) ABSTRACT Peterstown, WV (US) (73) Assignee: Celanese Acetate LLC, Irving, TX (US) A method for producing a polysaccharide ester microsphere may include forming a polysaccharide ester product from a (21) Appl. No.: 14/060,782 polysaccharide synthesis, wherein the polysaccharide ester (22) Filed: Oct. 23, 2013 product comprises a polysaccharide ester and a solvent, dilut e a? a 9 ing the polysaccharide ester product, thereby yielding a Related U.S. Application Data polysaccharide ester dope; and forming a plurality of polysaccharide ester microspheres from the polysaccharide (60) Provisional application No. 61/717,726, filed on Oct. ester dope. Suitable polysaccharides may include, but are not 24, 2012. limited to, starch, cellulose, hemicellulose, algenates, chito Publication Classification san, and any combination thereof. Esters thereof may be organic esters (e.g., acetate and the like), inorganic esters (51) Int. Cl. (e.g., Sulfonates and the like), or combinations thereof. Fur A2.3L. I./22 (2006.01) ther, the solids conent of the polysaccharide ester dope, in AOIN 25/34 (2006.01) Some instances, may be greater than about 16 wt %.

(1.1) POLYSACCHARDEESTER SYNTHESIS

--- (1.5) (12) : FILTRATION FINISHING PROCESS e------(OPTIONAL) (PRECIPITATION, WASHING, AND DRYING (1.4) DLUTION

FINISHED POLYSACCHARIDE ESTER

(1.3) (1.5) DOPE ; FILTRATION FORMATION (OPTIONAL)

POYSACCHARIDE ESTER DOPE

(1.6) FORM POLYSACCHARIDE ESTER MIRCOSPHERES Patent Application Publication Apr. 24, 2014 Sheet 1 of 15 US 2014/011382.6 A1

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US 2014/0113826 A1 Apr. 24, 2014

POLYSACCHARDE ESTERMICROSPHERES tions, alterations, combinations, and equivalents in form and AND METHODS AND ARTICLES RELATING function, as will occur to those skilled in the art and having the THERETO benefit of this disclosure. 0007 FIG. 1 provides nonlimiting examples of methods CROSS-REFERENCE TO RELATED for forming microspheres according to at least some embodi APPLICATIONS ments described herein. 0008 FIG. 2 provides an uptake profile for a cellulose 0001. This application claims priority to U.S. Provisional ester microsphere according to at least Some embodiments Patent Application No. 61/717,726 filed on Oct. 24, 2012. described herein. 0009 FIG. 3 provides SEM micrograph of several micro BACKGROUND spheres produced according to at least some embodiments 0002 The exemplary embodiments described herein described herein. relate to polysaccharide ester microspheres and methods and 0010 FIG. 4 provides SEM micrograph of several micro articles relating thereto. spheres produced according to at least some embodiments 0003. The most common polysaccharide ester to be used described herein. in microspheres is cellulose ester. Cellulose ester micro 0011 FIG. 5 provides SEM micrograph of several micro spheres are often Substantially rigid beads that consist essen spheres produced according to at least some embodiments tially of cellulose ester and have some degree of porosity described herein. based on the method with which they are produced. Cellulose 0012 FIG. 6 provides SEM micrograph of several micro ester microspheres have proven useful for immobilizing spheres produced according to at least some embodiments enzymes and release of chemicals, especially in conjunction described herein. with filter and chromatograph packing materials. Further, (0013 FIG. 7 provides SEM micrograph of several micro cellulose ester microspheres have found some industrial Suc spheres produced according to at least some embodiments cess in pharmaceutical and cosmetic applications. However, described herein. these applications, in addition to food, personal care, agricul 0014 FIG. 8 provides SEM micrograph of several micro tural applications, and others, would benefit from and/or be spheres produced according to at least some embodiments further enabled with the ability to produce cellulose ester described herein. microspheres at lower cost and with tailored properties (e.g., (0015 FIG. 9 provides SEM micrograph of several micro release rate of additives, solubility, polarity, and strength). spheres produced according to at least some embodiments 0004 Methods for forming cellulose ester microspheres described herein. include solvent evaporation methods, precipitation methods, 0016 FIG. 10 provides SEM micrograph of several micro and emulsion methods that utilize cellulose ester flake as the spheres produced according to at least some embodiments precursor. The production of cellulose ester flake can be described herein. energy intensive, especially in the finishing process that yield 0017 FIG. 11 provides SEM micrograph of several micro the dry flake after the reactions are completed. Further, these spheres produced according to at least some embodiments production methods generally provide for batch production described herein. of cellulose ester microspheres, which increases production 0018 FIG. 12 provides SEM micrograph of several micro cost, time, and waste. For industrial uses to be a reality, a spheres produced according to at least some embodiments continuous production process is desirable to reduce cost and described herein. increase product uniformity. (0019 FIG. 13 provides SEM micrograph of several micro 0005 Additionally, tailoring the properties of the cellu spheres produced according to at least some embodiments lose ester microspheres may enable a wider breadth of appli described herein. cations than have been previously realized. For example, 0020 FIG. 14 provides SEM micrograph of several micro cosmetics are increasingly using controlled release to deliver spheres produced according to at least some embodiments Vitamins and minerals and/or release fragrances over moder described herein. ate time periods, like a day. Similarly, additives for agricul 0021 FIG. 15 provides SEM micrograph of several micro tural applications (e.g., fertilizers and pesticides) are increas spheres produced according to at least some embodiments ingly being investigated for controlled and/or long-term described herein. efficacy with single or minimal treatments. Cellulose ester microspheres have been limited in the ability to adapt the DETAILED DESCRIPTION properties to a specific additive in combination with an appli 0022. The exemplary embodiments described herein cation. For example, a desired release rate may be similar relate to polysaccharide ester microspheres and methods and between a vitamin in a cosmetic application and a pesticide in articles relating thereto. an agricultural application, but the hardness and size for the 0023. As used herein, the term “microsphere' encom respective applications may be very different. Therefore, passes shapes that are spherical, Substantially spherical, multi-dimensional tailoring of properties and production on oblong, Substantially oblong, teardrop, Substantially tear an industrial-scale may be of value in expanding the practical drop, prolate spherical, Substantially prolate spherical, and applications of cellulose ester microspheres. the like, and any hybrid thereof. 0024. The polysaccharide ester microspheres described BRIEF DESCRIPTION OF THE DRAWINGS herein comprise at least one polysaccharide ester. The com 0006. The following figures are included to illustrate cer positional versatility of polysaccharide esters and ability to tain aspects of the exemplary embodiments described herein, mix various polysaccharide esters may allow for tailoring the and should not be viewed as exclusive embodiments. The properties (e.g., size, strength, morphology, solubility, and subject matter disclosed is capable of considerable modifica polarity) of the polysaccharide ester microspheres, which US 2014/0113826 A1 Apr. 24, 2014

may be useful in expanding the applications of polysaccha late), Substituted aromatic esters, and the like, any derivative ride ester microspheres. For example, tailoring the properties thereof, and any combination thereof. Without being limited of the polysaccharide ester microspheres may allow for by theory, it is believed that the organic ester substituent of the manipulating the release rates of additives (e.g., pharmaceu polysaccharide ester described herein may affect, interalia, ticals, flavors, nutraceuticals, plant nutrients, and insect repel the release rate of an additive from a polysaccharide ester lents) from the polysaccharide ester microspheres. microsphere described herein. 0025. Further, described herein are methods that facilitate 0031. In some embodiments, the degree of substitution of industrial production of polysaccharide ester microspheres the polysaccharide ester may range from a lower limit of with tailorable properties. For example, continuous produc about 0.2,0.4,0.6,0.8, 1, 1.5, 2, 2.3, or 2.5 to an upper limit tion methods may be employed to reduce the time, cost, and of less than about 3, 2.9, 2.7, 2.5, 2, or 1.5, and wherein the waste associated with their production and facilitates their degree of Substitution may range from any lower limit to any use in industrial applications. Additionally, in some embodi upper limit and encompass any Subset therebetween. As used ments, the polysaccharide ester microspheres may be pro herein, the term “degree of substitution” refers to the average duced directly from a dope extracted from the production of number of hydroxyl groups that have been replaced by the polysaccharide ester. That is, at least Some polysaccharide organic functional groups bound to an anhydroglucose unit, ester microsphere production methods do not require a fin which can be determined by a plurality of methods including ished form (e.g., flake) of the polysaccharide ester. By not chemical Saponification and titration, liquid chromatography, having to finish the polysaccharide ester, the associated time, NIR, and the like. In some embodiments, a polysaccharide cost, energy consumption, and chemical waste is reduced. ester may be cellulose diacetate having a degree of Substitu Accordingly, the polysaccharide ester microsphere produc tion ranging from about 2.2 to about 2.7. In some embodi tion methods described herein may, in some embodiments, ments, a polysaccharide ester may be cellulose triacetatehav advantageously have a significantly smaller environmental ing a degree of Substitution of about 2.7 or greater. impact while being cost effective for industrial scale-up. 0032. As used herein, the term “inorganic ester substitu 0026. It should be noted that when “about is used herein ent” refers to an ester that comprises an oxygenbound to an R in reference to a number in a numerical list, the term “about group and an inorganic, nonmetal atom (e.g., Sulfur, phos modifies each number of the numerical list. It should be noted phorus, boron, and chlorine). It should be noted that inorganic that in some numerical listings of ranges. Some lower limits esters encompass esters derived from oxoacids that comprise listed may be greater than Some upper limits listed. One both inorganic, nonmetal atoms and carbonatoms (e.g., alkyl skilled in the art will recognize that the selected subset will Sulfonic acids like methane sulfonic acid). Inorganic ester require the selection of an upper limit in excess of the selected Substituents may include, but are not limited to, hypochlorite, lower limit. chlorite, chlorate, perchlorate, Sulfite, Sulfate, Sulfonates (e.g., taurine, toluenesulfonate, C-Co alkyl Sulfonate, and I. Polysaccharide Ester Microsphere Compositions aryl Sulfonate), fluorosulfate, nitrite, nitrate, phosphite, phos 0027. Examples of suitable polysaccharide esters may phate, phosphonates, borate, and the like, any derivative include, but are not limited to, ester derivatives of starch, thereof, and any combination thereof. cellulose, hemicellulose, algenates, chitosan, and the like, 0033. In some embodiments, the weight percent of the and any combination thereof. Ester derivatives may be inorganic, nonmetal atom of the inorganic ester Substituent of organic esters Substituents, inorganic ester Substituents, or a a polysaccharide ester may range from a lower limit of about combination thereof. 0.01%, 0.05%, or 0.1% to an upper limit of about 8%, 5%, 0028. As used herein, the term “starch” refers to a natural 3%, 1%, 0.5%, 0.25%, 0.2%, or 0.15%, and wherein the polysaccharide that includes amylose and amylopectin in weight percent may range from any lower limit to any upper various ratios and derivatives thereof. Example of starches limit and encompass any Subset therebetween. may include, but are not limited to, waxy starches, modified 0034 Polysaccharide esters with inorganic ester substitu starches, native starches, dextrins, and maltodextrins with ents may be produced via several synthesis routes, at least dextrose equivalents of 1-50. Suitable starch sources for some of which are described in further detail in copending starchesters may, in Some embodiments, include, but are not International Patent Application No. PCT/US 12/56802 limited to, cereals, rice, wheat, maize, root vegetables, pota entitled “Substituted Cellulose Ester Adhesives and Methods toes, corn, tapioca, cassava, acorns, arrowroot, arracacha, and Articles Relating Thereto' filed on Sep. 24, 2012, the bananas, barley, breadfruit, buckwheat, canna, colacasia, entire disclosure of which is incorporated herein by reference. katakuri, kudzu, malanga, millet, oats, oca, polynesian arrow 0035 Tailoring the properties of the polysaccharide ester root, Sago, Sorghum, Sweet potatoes, rye, taro, chestnuts, microspheres described herein (e.g., average particle size, water chestnuts, yams, beans, favas, lentils, mung beans, particle size distribution, porosity, Solubility, and hardness) peas, chickpeas, and the like, and any combination thereof. may be achieved, in Some embodiments, by tailoring the 0029 Suitable cellulosic sources for cellulose esters may, properties of the at least one polysaccharide ester and, if more in some embodiments, include, but are not limited to, Soft than one, the relative ratios thereof. Properties of the polysac woods, hardwoods, cotton linters, Switchgrass, bamboo, charide esters that may, in Some embodiments, be useful to bagasse, industrial hemp, willow, poplar, perennial grasses tailor may include, but are not limited to, the organic ester (e.g., grasses of the Miscanthus family), bacterial cellulose, Substituent, degree of Substitution, composition and amount seed hulls (e.g., soybeans), and the like, and any combination of additional Substituents (e.g., inorganic ester Substituents), thereof. molecular weight, solubility, hydrophobicity, and the like, 0030 The organic ester substituent may include, but are and any combination thereof. not limited to, C-C aliphatic esters (e.g., acetate, propi 0036. In some embodiments, the polysaccharide ester onate, or butyrate), functional C-Co aliphatic esters (e.g., microspheres described herein may comprise two or more acrylates or diesters), aromatic esters (e.g., benzoate orphtha types of polysaccharide esters. As used herein, types of US 2014/0113826 A1 Apr. 24, 2014

polysaccharide esters may be differentiated by at least one sition and amount of inorganic ester Substituents affects the property of the polysaccharide ester (e.g., composition and Solvent selection. By way of nonlimiting example, a polysac amount of organic ester Substituent(s), composition and charide ester (e.g., cellulose acetate) with a degree of Substi amount of inorganic ester Substituent(s), molecular weight, tution of about 0.4 to about 1.2 may be soluble in water. By composition of the polysaccharide, and the like). In some way of another nonlimiting example, a polysaccharide ester embodiments where two or more types of polysaccharide having a degree of substitution of about 0.7 to about 2.7 and esters are used, the amount of each polysaccharide ester may a sulfate inorganic ester substituent with about 0.006% to independently range from a lower limit of greater than 0%. about 5% sulfur by weight may be soluble in a mixed solvent about 1%, 10%, 25%, or 50% by weight of the total polysac that comprises an aqueous solvent and an organic Solvent charide esters to an upper limit of about 99%, 90%, 75%, or (e.g., acetone). 50% by weight of the total polysaccharide esters, and wherein 0040. In some embodiments, the hydrophobicity of the the amount of each polysaccharide ester may independently polysaccharide esters may be modified or tuned to affect final range from any lower limit to any upper limit and encompass material properties. Hydrophobicity may be measured by any subset therebetween. forming a film of the polysaccharide ester and measuring the 0037. Without being limited by theory, it is believed that contact angle of water thereon. the chemical composition the polysaccharide esters (e.g., the 0041 Tailoring the properties of the polysaccharide esters composition and degree of substitution of an organic Substitu described herein may be achieved, in Some embodiments, ent and the composition and amount of an inorganic Substitu through adjustment in, interalia, the conditions of synthesis, ent) may affect, interalia, the release rate of an additive (e.g., the polysaccharide material from which the polysaccharide a dye, a pharmaceutical, a nutraceutical, a pesticide, and the esters are synthesized, and any combination thereof. like) from a polysaccharide esters microsphere, the uptake rate of an additive (e.g., a dye, a contaminant, and the like) II. Methods of Producing Polysaccharide Ester Microspheres into a polysaccharide esters microsphere, the crystallinity of a polysaccharide esters microsphere, the hydrophobicity of a 0042. Referring to FIG. 1, in some embodiments, forming polysaccharide esters microsphere, and the solubility of a polysaccharide ester microspheres described herein may pro polysaccharide esters microsphere. By way of nonlimiting ceed by a series of reactions that include synthesizing the example, polysaccharide esters microspheres comprising a polysaccharide ester (1.1), which may be by a variety of polysaccharide ester with a degree of substitution of about 2.7 methods depending on the desired composition, to yield a or greater may have a high crystallinity and a reduced rate of polysaccharide ester product. The polysaccharide ester prod release for an additive disposed therein as compared to a uct may then be processed in one of two general methods. The polysaccharide ester having a degree of Substitution of about first method includes the more traditional preparation method 2.2 to about 2.7. By way of another nonlimiting example, the of a finishing process (1.2) that precipitates the polysaccha properties of the polysaccharide ester microspheres may be ride ester product from the solvent of the synthesis reaction tailored by adjusting the ratio two or more polysaccharide (e.g., a mixture of acetic acid and water), washing the pre esters. By way of yet another nonlimiting example, lower cipitated polysaccharide ester, and drying the polysaccharide degrees of substitution may allow for additives capable of ester into a finished polysaccharide ester, which may be in a hydrogen bonding to diffuse more slowly through the powder or flake form, for example. Then, in dope formation polysaccharide ester and, consequently, release from a (1.3), the finished polysaccharide ester may then be dissolved polysaccharide esters microsphere at a lower rate than other into a solvent to yield a polysaccharide ester dope. The additives. polysaccharide ester dope may then be formed into polysac 0038. In some embodiments, the average molecular charide ester microspheres (1.6). weight of a polysaccharide ester described herein may be 0043 Alternatively, the polysaccharide ester product may about 1,000,000 g/mol or less, about 100,000 g/mol or less, or beformed directly into a dope by dilution (1.4) of the polysac more preferably about 50,000 g/mol or less. In some embodi charide ester product from the polysaccharide ester synthesis ments, the average molecular weight of a polysaccharide (1.1). Optionally before or after dilution, the solution may be ester may range from a lower limit of about 1,000 g/mol, filtered (1.5) (optionally with the addition of filter aids) to 5,000 g/mol, 10,000 g/mol, 25,000 g/mol, 50,000 g/mol, or remove, for example, unreacted polysaccharide and salts 100,000 g/mol to an upper limit of about 1,000,000 g/mol, formed during the polysaccharide ester synthesis (1.1). The 500,000 g/mol, 250,000 g/mol, 100,000 g/mol, or 50,000 polysaccharide ester dope may then be formed into polysac g/mol, and wherein the average molecular weight may range charide ester microspheres (1.6). from any lower limit to any upper limit and encompass any 0044. It should be noted that polysaccharide ester dopes subset therebetween. As used herein, the term “average may be produced with more than one polysaccharide ester molecular weight” refers to the number average molecular described herein by adding two or more polysaccharide esters weight as determined by gel permeation chromatography together during any stage between polysaccharide ester Syn using a polystyrene standard. thesis (1.1) and polysaccharide ester microsphere formation 0039. In some embodiments, the polysaccharide ester may (1.6). Further, the individual polysaccharide esters in be soluble in water, acetone, acetic acid, methylene chloride, embodiments with two or more polysaccharide esters in a dimethyl sulfoxide, dimethyl carbonate, dimethyl forma polysaccharide ester dope may be produced and/or treated by mide, N-methylpyrrolidone, mixtures thereof, and the like. any suitable methods including those described herein. For As used herein, the term “soluble' refers to a substantially example, a first polysaccharide ester may be synthesized and dissolved, single phase, and homogeneous Substance that then treated by a finishing process (1.2) and a dope formation may have a small fraction (e.g., less than about 1%) of the (1.3), while a second polysaccharide ester may be synthe Substance being a semi-soluble (e.g., a gel). One skilled in the sized and diluted (1.4) with the polysaccharide ester dope art will know that the degree of substitution and the compo comprising the first polysaccharide ester. In another example, US 2014/0113826 A1 Apr. 24, 2014

two polysaccharide ester products may be mixed, filtered should recognize that the need for and amount of filtration (1.5), diluted (1.4), and filtered (1.5) again to yield a polysac may be influenced by, inter alia, the polysaccharide starting charide ester dope. material, the desired purity of the polysaccharide ester micro 0045 Referring to the dope formation process (1.3) and spheres, the application of the polysaccharide ester micro the dilution process (1.4), Suitable dope solvents may include, spheres, the desired properties of the polysaccharide ester but are not limited to, acetic acid, water, methanol, ethanol, microspheres, and the like. propanol, acetone, nitromethane, dioxane, tetrahydrofuran, 0050 Referring to the microsphere forming process (1.6), pyridine, methyl ethyl ketone, dimethyl sulfoxide, methyl forming polysaccharide ester microspheres described herein acetate, dichloromethane, chloroform, tetrachloroethane, may, in Some embodiments, involve forming droplets of a trichloroethane, dimethyl sulfoxide, dimethyl formamide, polysaccharide ester dope and coagulating the droplets into dimethyl carbonate, ethylene carbonate, propylene carbon microspheres in a coagulation bath. In some embodiments, a ate, and the like, and any combination thereof. coagulation bath may comprise a non-solvent as described 0046. In some embodiments, the dope formation process above in relation to the dope formation process (1.3) and the (1.3) and the dilution process (1.4) may also utilize a non dilution process (1.4). It should be noted that the non-solvent Solvent that may assist in forming the polysaccharide ester utilized to form the polysaccharide ester dope and the non microspheres. In some embodiments, suitable dope non-sol solvent of the coagulation bath may be the same or different. vents may include, but are not limited to, acetic acid, water, 0051. In some embodiments, forming droplets may methanol, ethanol, propanol, acetone, nitromethane, dioxane, involve methods that include, but are not limited to, spher tetrahydrofuran, pyridine, methyl ethyl ketone, dimethylsul onizing, aerosol spraying, airless spraying, ultrasonic spray foxide, dimethyl carbonate, propylene carbonate, ethylene ing, rotating disk spraying, dripping, impinging on rotating carbonate, methyl acetate, dichloromethane, chloroform, tet atomizer plates, and the like, any hybrid thereof, and any rachloroethane, trichloroethane, and the like, and any combi combination thereof. In some embodiments, such methods nation thereof. One skilled in the art with the benefit of this may utilize double nozzles that enable formation of core-shell disclosure should recognize that the properties of the polysac microspheres. In some embodiments, the core and/or the shell charide ester product will, interalia, determine suitable dope of a core shell microspheres may comprise a polysaccharide Solvents. ester described herein. 0047. By way of nonlimiting example, polysaccharide 0052. In some embodiments, the polysaccharide ester esters having a degree of Substitution of about 2.5 may utilize dope may comprise salts, which may affect the morphology, acetone as a solvent and water as a non-solvent in the polysac surface roughness, diameter, and the like of the polysaccha charide ester dope, where polysaccharide esters having high ride ester microspheres produced. In some instances, the salts degrees of Substitution may utilize acetic acid as the solvent may be present as a result of using a polysaccharide ester and water as the non-solvent. In some embodiments, a non product without finishing. In some instances, the salts may be Solvent may be present in a polysaccharide ester dope in an added to the polysaccharide ester dope. A hybrid of the fore amount ranging from a lower limit of 0%, about 0.1%, 1%, 5%, or 10% by weight of the solvent to an upper limit of about going is also envisioned. 40%, 30%, 20%, 15%, or 10% by weight of the solvent, and 0053 Examples of salts may include, but are not limited wherein the amount of non-solvent may range from any lower to, sodium, potassium, magnesium, calcium, and the like salts limit to any upper limit and encompass any Subset therebe of inorganic acids or organic acids, including combinations tWeen thereof (e.g., chlorides, bromides, Sulfates, phosphate, 0048. In some embodiments, the polysaccharide ester acetates, formates, and the like). dope described herein may have a solids concentration of 0054. In some embodiments, a coagulation bath may com about 50% by weight or less, about 30% by weight or less, or prise Surfactants that participate in the formation of the about 25% by weight or less. In some embodiments, the polysaccharide ester microspheres and may affect the mor polysaccharide ester dope described herein may have a solids phology and/or diameter of the polysaccharide ester micro concentration ranging from a lower limit of about 4%, 6%, spheres produced. In some embodiments, a polysaccharide 8%, 10%, 12%, or 15% to an upper limit of about 50%, 40%, ester dope may comprise Surfactants that participate in the 30%, 25%, 18%, 16%, 14%, or 12% by weight, and wherein formation of the polysaccharide ester microspheres and may the solids concentration may range from any lower limit to affect the morphology and/or diameter of the polysaccharide any upper limit and encompasses and Subset therebetween. ester microspheres produced. Inclusion of Surfactants in the 0049 Referring to the filtration process (1.5), filtration polysaccharide ester dope may improve raw material usage or may, in some embodiments, remove unwanted components, product uniformity. unreacted polysaccharide material, reaction byproducts, and 0055 Examples of surfactants may, in some embodi any combination thereof from the polysaccharide ester prod ments, include, but are not limited to, TWEENSR) (polyoxy uct. For example, salts like magnesium Sulfate, calcium Sul alkylene derivatives of hexitol anhydride partial long chain fate, or ammonium Sulfate may, in some embodiments, be fatty acid esters, available from Sigma Aldrich), SPANS(R) produced in the esterification and/or hydrolysis reactions. (partial esters of common fatty acids such as caloric, palmitic, Further, in Some embodiments, unreacted polysaccharide Stearate, and oleic acids, and hexitol anhydrides, available material (e.g., cellulose fibers) may also be removed from a from Sigma Aldrich), NIA-PROOF(R) #4 (sodium tetradecyl polysaccharide ester product described herein via filtration. sulfate, available from Niacet Corporation), polyethylene As described above, the filtration process (1.5) is optional. glycols, ethylene glycol-propylene glycol-ethylene glycol For example, with some dissolving-grade cellulose starting triblock copolymers, fatty alcohol ethoxylates, Cs-Co Sul materials, the polysaccharide ester synthesis (1.1) may be fates, Cs-Co Sulfonates, Cs-Cophosphates, Cs-Cocarboxy Sufficiently clean to produce a Suitable polysaccharide ester lates, TRITONSR (surfactants with hydrophilic polyethylene dope. One skilled in the art with the benefit of this disclosure oxide chains and hydrophobic aromatic hydrocarbons, avail US 2014/0113826 A1 Apr. 24, 2014 able from Sigma Aldrich), fatty acid ethoxylates, aromatic any lower limit to any upper limit and encompass any Subset acid ethoxylates, and the like, any derivative thereof, and any therebetween. As used herein, the term “average pore size” combination thereof. refers to the pore volume measured with BET analysis with 0056. In some embodiments, the distance between droplet nitrogen gas, which is sometimes referred to as the average formation and the coagulation bath may affect the morphol micropore size. The term “average pore size” does not refer to ogy and/or porosity of the polysaccharide ester microspheres the size of the macropores measured by visualization, for produced. For example, the distance between droplet forma example, with a scanning electron micrograph. tion and the coagulation bath may, in some embodiments, 0063. In some embodiments, the polysaccharide ester range from about 20 inches to about 100 inches. microspheres may have a crystallinity ranging from a lower 0057. In some embodiments, the temperature of the limit of about 0%. 5%, or 10% to an upper limit of about 70%, microsphere forming process (1.6) (including portions 60%, 50%, or 40%, and wherein the crystallinity may range thereof like the dope temperature, ambient temperature, and from any lower limit to any upper limit and encompass any coagulation bath temperature) may also affect the morphol subset therebetween. One suitable method for determining ogy and/or porosity of the polysaccharide ester microspheres porosity is X-ray diffraction. produced. For example, the temperature of dope and/or the 0064. In some embodiments, the polysaccharide ester coagulation bath may, in some embodiments, independently microspheres may have a crush strength ranging from a lower range from about 15° C. and about 90° C. Further, in some limit of about 5 g, 7g, 10g, or 15 g to an upper limit of about embodiments, the temperature of the dope and the coagula 45 g, 30g, 25g, 20g, or 15 g as the mass required to produce tion bath may be the same or different. a 10% loss in particle diameter, and wherein the crash 0058. After formation, the polysaccharide ester micro strength may range from any lower limit to any upper limit spheres may be removed from the coagulation bath, washed, and encompass any Subset therebetween. One Suitable and dried. In some embodiments, the microsphere forming method for determining crush strength is ASTM D3102-72. process (1.6) and Subsequent washing and drying processes 0065. In some embodiments, the polysaccharide ester may be a continuous process, a batch process, or a hybrid microspheres may have an average particle size ranging from thereof. For example, polysaccharide ester microspheres may a lower limit of about 100 nm, 250 nm, 500 nm, 1 micron, 5 be continuously formed and transferred continuously from microns, 25 microns, or 100 microns to an upper limit of the coagulation bath, e.g., by conveyor, through areas that about 2000 microns, 1000 microns, 750 microns, 500 provide washing and drying of the polysaccharide ester microns, 250 microns, or 100 microns, and wherein the aver microspheres. Continuous processing may advantageously age particle size may range from any lower limit to any upper reduce both labor and manufacturing costs and, in some limit and encompass any subset therebetween. Suitable meth instances, increase the production speed. Further, in some ods for determining average particle size include sieve tech embodiments, continuous processes may have at various niques for larger particle sizes and laser diffraction analyzers points along the process quality control measures enacted. for Smaller particle sizes. As used herein, the term "average 0059 Properties of the polysaccharide ester microspheres particle size” refers to the Ds by weight (i.e., the diameter that may, in some embodiments, be useful to tailor may where 50% by weight of the microspheres have a lower diam include, but are not limited to, porosity, crystallinity, crush eter). strength, Surface area, particle size, dye uptake, polarity, 0066. In some embodiments, the polysaccharide ester hydrophobicity, release rate of an additive from the polysac microspheres may have a dye uptake ranging from a lower charide ester microspheres, morphology, degradation, and limit of about 0.1 g, 0.5g, or 1 g per 100 g of polysaccharide the like, and any combination thereof. ester microspheres per 4 hours to an upper limit of about 5 g, 0060. In some embodiments, the surface area of the 3 g, or 2g per 100g of polysaccharide ester microspheres per polysaccharide ester microspheres may range from a lower 4 hours as measured using Acid Blue 290, and wherein the limit of about 1 m/g, 5 m/g, 10 m/g, or 15 m/g to an upper dye uptake may range from any lower limit to any upper limit limit of about 50 m/g, 40 m/g, 30 m/g, or 25 m/g, and and encompass any Subset therebetween. wherein the Surface area may range from any lower limit to 0067. In some embodiments, polysaccharide ester micro any upper limit and encompass any Subset therebetween. The spheres may optionally further comprise additives. Exem surface area may be measured with BET analysis with nitro plary additives may include, but are not limited to, plasticiz gen gas. ers, dyes, pigments, pore forming agents, active 0061. In some embodiments, the total pore volume of the pharmaceuticals (e.g., hydrophilic active pharmaceutical, polysaccharide ester microspheres may range from a lower hydrophobic active pharmaceutical, amphoteric active phar limit of about 0.05 mL/g, 0.07 mL/g, or 0.1 mL/g to an upper maceutical, pain relievers, antibiotics, steroids, and antioxi limit of about 0.15 mL/g, 0.12 mL/g, or 0.1 mL/g, and dants), prodrugs of active pharmaceuticals, active biologicals wherein the pore Volume may range from any lower limit to (e.g., hormones, DNAS, RNAS, siRNAS, peptides, enzymes, any upper limit and encompass any Subset therebetween. As nucleotides, oligionucleotides, antibodies, and monoclonal used herein, the term “pore volume refers to the pore volume antibodies), antibiotics, antifungals, antitoxins, antigens, measured with BET analysis with nitrogen gas, which is therapeutics (e.g., chemotherapeutics, radiation-poisoning sometimes referred to as the micropore volume. The term therapeutics, radioisotopes), preventive therapeutics (e.g., "pore volume' does not refer to the volume of the macropores antioxidants, radiation mitigation agents, and vaccines), measured by visualization, for example, with a scanning elec nutritional Supplements (e.g., vitamins, minerals, nutraceuti tron micrograph. cals, metabolism enhancing agents, and antioxidants), imag 0062. In some embodiments, the average pore size of the ing agents (e.g., magnetic resonance imaging contrast agents, polysaccharide ester microspheres may range from a lower X-ray imaging contrast agents, and radioisotopes), food limit of about 20 nm or 25 nm to an upper limit of about 30 nm agents (e.g., preservatives, probiotics, enzymes, colors, pig or 25 nm, and wherein the average pore size may range from ments, Sweeteners, water, flavorants, and aromas), flavorants, US 2014/0113826 A1 Apr. 24, 2014 olfactory agents (e.g., fragrances and aromas), plant agents additive. This may advantageously allow for higher doses (e.g., agricultural active ingredients, pesticides, fertilizers, and/or longer lifetime articles. and hormones), chemical-reaction agents (e.g., chemical 0073. By way of another nonlimiting example, an oral crosslinkers and catalysts), insect repellents, and the like, and pharmaceutical delivery vehicle (e.g., a tablet, a capsule, or a any combination thereof. Nonlimiting examples of at least liquid-gel) may, in some embodiments, comprise polysaccha some of these additives are provided herein. ride ester microspheres described herein. The polysaccharide 0068 Additives may in some embodiments, be included in ester microspheres in this and other similar applications may, a polysaccharide ester dope described herein. In some in some embodiments, advantageously comprise an additive embodiments, additives may be absorbed into and/or adsorb to be released (e.g., an active pharmaceutical, a nutraceutical, to polysaccharide ester microspheres after the forming pro and the like described herein) and function to control the cess (1.6). Combinations of the aforementioned may be suit release rate of the additive. In some embodiments, the deliv able in Some embodiments. In continuous processes ery vehicle may function to control the release of the micro described herein, areas for the incorporation of additives may capsules, thereby enabling, in Some embodiments, a higher optionally be included. degree of release timing and release rate of the additive. 0069 Polysaccharide ester microspheres may have a com 0074 By way of yet another nonlimiting example, an agri bination of the properties described herein (e.g., crystallinity, cultural product (e.g., a spray, a concentrate, or the like) may crush strength, Surface area, average particle size, particle comprise polysaccharide ester microspheres described herein size distribution, dye uptake, and the like) and comprise at dispersed in a fluid (e.g., water or an emulsion). The polysac least one polysaccharide ester described herein (e.g., based on charide ester microspheres in this and other similar applica molecular weight, organic ester Substituent, degree of Substi tions may, in some embodiments, advantageously comprise tution, inorganic ester Substituent and amount thereof, hydro plantagents like herbicides, fungicides, insecticides, bacteri phobicity, and the like) and optionally further comprise at cides, nitrogen sources, growth promoters, and the like, and least one additive described herein. Such polysaccharide ester any combination thereof. In some embodiments, the polysac microspheres may be formed by any suitable method charide ester microspheres may be designed so as to change described herein (e.g., batch, continuous, or hybrid methods the release rate with changes in pH. In some embodiments, in combination with methods for producing dopes that the polysaccharide ester microspheres may be designed to include or exclude finishing processes (or that produce dopes have an increased release rate after a rain and/or watering, from multiple methods that independently include or exclude e.g., due to a concentration differential and the Surrounding finishing processes)). environment. 0075. By way of another nonlimiting example, a food or III. Applications and Articles Comprising Polysaccharide beverage product may, in some embodiments, comprise Ester Microspheres polysaccharide ester microspheres described herein. The 0070. In some embodiments, polysaccharide ester micro polysaccharide ester microspheres in this and other similar spheres described herein may be utilized for the controlled applications may, in some embodiments, comprise additives release of additives, e.g., active pharmaceuticals, prodrugs of like flavorants, aromas, and/or colorants and serve to provide active pharmaceuticals, active biologicals, antibiotics, anti for a desired quality (e.g., color, flavor, and/or aroma inten fungals, antitoxins, antigens, therapeutics, preventive thera sity) of the food or beverage product over an extended time peutics, nutritional Supplements, imaging agents, food frame (e.g., to better match the preservative lifetime of the agents, flavorants, olfactory agents, plant agents, chemical food or beverage product). The polysaccharide ester micro reaction agents, insect repellents, and the like, and any com spheres in this and other similar applications may, in some bination thereof. embodiments, comprise additives like flavorants, aromas, 0071. In some embodiments, articles may comprise and/or colorants and serve to provide for release of a color, polysaccharide ester microspheres described herein. Exem flavor, and/or aroma upon rupture (e.g., during chewing) plary examples of articles Suitable for use in conjunction with (e.g., gums that change the color of the tongue or release polysaccharide ester microspheres may include, but are not different flavors when chewed, dissolvable strips, meal-re limited to, pharmaceutical compositions (e.g., excipients and placement products, ice creams, and the like). The polysac patches), cosmetics compositions (e.g., liquids, creams, charide ester microspheres in this and other similar applica lotions, sprays, lipstick, color cosmetics, and mascara), agri tions may, in Some embodiments, comprise additives like cultural compositions (e.g., plant nutritional Supplements and Vitamins, nutraceuticals, pharmaceutical, and the like and pesticide compositions), food products (e.g., flavorant serve to enhance the nutritional value of or deliver pharma enhancers, aroma enhancers, nutritional enhancers), ballistic ceuticals via the food or beverage product (e.g., dissolvable applications such as explosives and propellants, filters (e.g., strips, candy products, powdered beverage mixes, yogurts, cigarette filters, air filters, and water filters), filter packing, granola bars, meal-replacement products, nicotine gums, and chromatographic packing, specialty filters, any hybrid the like). In some embodiments, combinations of the forego thereof, and the like. ing additives and/or combinations of the foregoing polysac 0072 By way of nonlimiting example, a pharmaceutical charide ester microspheres may be Suitable for use in con patch may, in Some embodiments, comprise in order a back junction with food or beverage products. ing layer, an active layer that comprises polysaccharide ester 0076. By way of yet another nonlimiting example, a food microspheres described herein, and an adhesive layer. The or beverage packaging may, in some embodiments, comprise polysaccharide ester microspheres in this and other similar polysaccharide ester microspheres described herein. The applications may, in some embodiments, advantageously polysaccharide ester microspheres in this and other similar comprise high concentrations of an additive to be released applications may, in some embodiments, comprise additives (e.g., an active pharmaceutical, a nutritional Supplement, and like aromas and be incorporated into the packaging so as to the like described herein) and function as a reservoir for the release an aroma burst upon opening the package (e.g., in an US 2014/0113826 A1 Apr. 24, 2014

adhesive seal). The polysaccharide ester microspheres in this material of the filter (e.g., the cellulose acetate tow, the paper, and other similar applications may, in some embodiments, or the like). In some instances, the cigarette filter may com comprise additives like flavorants and/or aromas and be prise a cavity and/or a capsule with the microspheres con incorporated into the edible packaging so as to release the tained therein. In some instances, a hybrid of the foregoing additive upon chewing or dissolution of the packaging (e.g., may be useful. The polysaccharide ester microspheres in this edible gum wrappers). and other similar applications may, in some embodiments, 0077. By way of another nonlimiting example, a cosmetic comprise additives like aromas, flavorants, and the like. In (e.g., bronzers, face powder, eye shadow, eyeliner, mascara, Some embodiments, the act of drawing on the cigarette filter blush, brow powder, baby powder, lip-gloss, lipstick, and the may decrease the air pressure about the polysaccharide ester like) may, in Some embodiments, comprise polysaccharide microspheres, thereby increasing the release of the additive ester microspheres described herein. The polysaccharide therein. ester microspheres in this and other similar applications may, I0082. By way of another nonlimiting example, an explo in some embodiments, comprise additives like colorants, fla sive device and/or a propellant may, in some embodiments, Vorants, aromas, deodorants, nutraceuticals, and the like. In comprise polysaccharide ester microspheres described Some embodiments, the ability of polysaccharide ester micro herein. The polysaccharide ester microspheres in this and spheres to uptake and hold a high concentration of the colo other similar applications may, in Some embodiments, com rant, which may be particularly advantageous in cosmetics prise additives like an explosive material, a fuel material, a with intense colors (e.g., eye shadows, blushes, bronzers, fuel additive, and the like. In some embodiments, the polysac lip-glosses, lipsticks, and the like. Further, in Some embodi charide ester microspheres in this and similar applications ments, it has been observed that polysaccharide ester micro may be designed to increase release under mechanical pres spheres described herein may provide a luster to the surface to Sure, which may act as a trigger for explosive device and/or which they are applied, which may be advantageous in cos propellant while enabling safe transport otherwise. metic powder applications. I0083. By way of yet another nonlimiting example, an 0078. By way of yet another nonlimiting example, a lotion adhesive may, in some embodiments, comprise polysaccha or cream may, in Some embodiments, comprise polysaccha ride ester microspheres described herein. In some embodi ride ester microspheres described herein. The polysaccharide ments, the polysaccharide ester microspheres may be utilized ester microspheres in this and other similar applications may, as a substitute for tackifiers and/or viscosity modifiers in in Some embodiments, comprise additives like colorants (e.g., adhesives and optionally comprise an additive useful in a for bronzing), aromas, deodorants, nutraceuticals, and the desired application (e.g., a pharmaceutical for the adhesive in like. In some embodiments, polysaccharide ester micro transdermal patch, an aroma in a food packaging adhesive, spheres Suitable for use in conjunction with lotions may be and the like). Smaller in size to minimize or eliminate an associated feel I0084. In some embodiments, the polysaccharide ester (e.g., about 50 microns or less) or may be larger (e.g., greater microspheres described herein may be administered to a than about 50 microns) to elicit an abrasive feel (e.g., in patient. As used herein, the term “subject' and “patient” are exfoliating lotions or creams). used interchangeably herein and refer to both human and 0079. By way of another nonlimiting example, a hair prod nonhuman animals and insects. The term “nonhuman ani uct (e.g., shampoo, conditioner, oil, dye, and the like) may, in mals' as used herein includes all vertebrates, e.g., mammals Some embodiments, comprise polysaccharide ester micro and non-mammals, such as nonhuman primates, mice, rats, spheres described. The polysaccharide ester microspheres in sheep, dogs, cats, horses, cows, chickens, amphibians, fish, this and other similar applications may, in some embodi reptiles, and the like. The term “insects” as used herein ments, comprise additives like colorants, aromas (e.g., essen includes all arthropods, e.g., bees, flies, Drosophila flies, tial oils), deodorants, moisturizers, nutraceuticals (e.g., vita beetles, spiders, and the like. min E), and the like. I0085. In some embodiments, the polysaccharide ester 0080. By way of another nonlimiting example, a deodor microspheres described herein may be administered to ant (e.g., sprays, roll-on, powders, and the like) may, in some patients orally (e.g., pills, tablets, and the like), Subdermally embodiments, comprise polysaccharide ester microspheres (e.g., Subdermal implants), transdermally (e.g., patches, described herein. The polysaccharide ester microspheres in lotions, cosmetics, and the like), transmucosally (e.g., oro this and other similar applications may, in some embodi mucosal inserts, intrauterine devices, intravaginal rings, den ments, comprise additives like aromas (e.g., essential oils), tal fibers, and the like), and/or as a part of an implantable deodorants, moisturizers, nutraceuticals (e.g., vitamin E), and medical device. In some embodiments, additives in polysac the like. In some embodiments, the polysaccharide ester charide ester microspheres may be administered to patients microspheres may be designed to be abrasion activated (e.g., by oral delivery of the polysaccharide ester microspheres, increase release under mechanical pressure) so as to increase Subdermal implantation or injection of the polysaccharide release of the additive when activity increases. In some ester microspheres, placement of the polysaccharide ester embodiments, the polysaccharide ester microspheres may be microspheres for transdermal administration of the additive, designed to increase release based on pH so as to increase and/or implanting a medical device including polysaccharide release of the additive when the local environments pH ester microspheres described herein. changes (e.g., during Sweating). 0086 A typical dosage of an additive (e.g., active pharma 0081. By way of yet another nonlimiting example, a ciga ceuticals and prodrugs of active pharmaceuticals) might rette filter may, in some embodiments, comprise polysaccha range from about 0.001 mg/kg to about 1000 mg/kg, prefer ride ester microspheres described herein. In some instance, ably from about 0.01 mg/kg to about 100 mg/kg, and more the cigarette filter may be a cellulose acetate tow filter, a paper preferably from about 0.10 mg/kg to about 20 mg/kg, relative filter, or the like with the polysaccharide ester microspheres to weight of the patient. In some embodiments, active phar dispersed throughout the filter, optionally adhered to the maceuticals and prodrugs of active pharmaceuticals may be US 2014/0113826 A1 Apr. 24, 2014

used alone or incombination with other additives. One skilled Yellow K-GL liquid, CARTASOL(R) Orange K-3GL liquid, in the art should understand the dose and/or combination of CARTASOL(R) Scarlet K-2GL liquid, CARTASOL(R) Red additives should be chosen so as to minimize adverse inter K-3BN liquid, CARTASOL(R) Blue K-5R liquid, CARTA actions. SOLOR. Blue K-RL liquid, CARTASOL(R) Turquoise K-RL 0087. In some embodiments, the polysaccharide ester liquid/granules, CARTASOLR) Brown K-BL liquid), FAS microspheres described herein may be a component of a kit. TUSOL(R) dyes (an auxochrome, available from BASF) (e.g., In some embodiments, a kit may include a set of instructions Yellow 3GL, Fastusol C Blue 74L), and the like, any deriva and at least one type of polysaccharide ester microspheres. In tive thereof, and any combination thereof. Some embodiments, a kit may include a set of instructions and 0091 Examples of pore forming agents may include, but an article comprising at least one type polysaccharide ester are not limited to, polyethylene glycol, triacetin, dimethyl microsphere described herein. phthalate, ethylene diacetate, Sorbitol, magnesium sulfate, IV. Additives and the like, and any combination thereof. 0092. Examples of suitable agents (active agents (e.g., 0088 Exemplary additives may include, but are not lim active pharmaceuticals and prodrugs of active pharmaceuti ited to, plasticizers, dyes, pigments, pore forming agents, cals), removal agents, and tracking agents) may include, but active pharmaceuticals (e.g., hydrophilic active pharmaceu are not limited to, 16-alpha fluoroestradiol. 16-alpha-gitoxin, tical, hydrophobic active pharmaceutical, amphoteric active 16-epiestriol, 17-alpha dihydroequilenin, 17-alpha estradiol, pharmaceutical, pain relievers, antibiotics, steroids, and anti 17-beta estradiol, 17-hydroxy progesterone, 1-alpha-hydrox oxidants), prodrugs of active pharmaceuticals, active biologi yvitamin D2, 1-dodecpyrrolidinone, 20-epi-1.25 dihydrox cals (e.g., hormones, DNAs, RNAs, siRNAs, peptides, yvitamin D3, 22-oxacalcitriol. 2CW. 2'-nor-cGMP 3-isobu enzymes, nucleotides, oligionucleotides, antibodies, and tyl GABA, 5-ethynyluracil, 6-FUDCA, 7-methoxytacrine, monoclonal antibodies), antibiotics, antifungals, antitoxins, abamectin, , abcizimab (commercially available as antigens, therapeutics (e.g., chemotherapeutics, radiation REOPROR) from Eli Lilly and Company), abecarnil, abirater poisoning therapeutics, radioisotopes), preventive therapeu one, ablukast, ablukast Sodium, acadesine, acamprosate, tics (e.g., antioxidants, radiation mitigation agents, and vac acarbose, , acecainide hydrochloride, aceclidine, cines), nutritional Supplements (e.g., vitamins, aceclofenae, acedapsone, aceglutamide aluminum, aceman nutraceuticals, metabolism enhancing agents, and antioxi nan, acetaminophen, acetazolamide, acetohexamide, aceto dants), imaging agents (e.g., magnetic resonance imaging hydroxamic acid, acetomepregenol, maleate, contrast agents, X-ray imaging contrast agents, and radioiso acetosulfone sodium, acetylcholine chloride, acetylcysteine, topes), food agents (e.g., preservatives, fragrances, and aro acetyl-L-carnitine, acetylmethadol, acifran, acipimox, mas), flavorants, olfactory agents (e.g., fragrances and aro acitemate, acitretin, acivicin, aclarubicin, aclatonium, acoda mas), plant agents (e.g., agricultural active ingredients, Zole hydrochloride, aconiazide, acrisorcin, acrivastine, acro pesticides, fertilizers, and hormones), chemical-reaction nine, actisomide, actodigin, acyclovir, acylfulvene, agents (e.g., chemical crosslinkers and catalysts), insect adafenoxate, adalimumab (commercially available as repellents, and the like, and any combination thereof. HUMIRAR) from Abbott Laboratories), adapalene, ada 0089. Examples of plasticizers may include, but are not palene, adatanserin, adatanserin hydrochloride, adecypenol, limited to, water, glycerol triacetate (triacetin), diacetin, tri adecypenol, adefovir, adelmidrol, ademetionine, adenosine, ethylcitrate, acetyl trimethylcitrate, dimethoxy-ethyl phtha adinazolam, adipheinine hydrochloride, adiposin, adoZe late, dimethyl phthalate, diethyl phthalate, dibutyl phthalate, lesin, adrafinil, adrenalone, airbutamine, alacepril, alamecin, diaryl phthalate, methyl phthalyl ethyl glycolate, o-phenyl alanine, alaproclate, alaptide, albendazole, albolabrin, phenyl-(bis) phenyl phosphate, 1,4-butanediol diacetate, albuterol (commercially available as VENTOLINR) from diacetate, dipropionate ester of triethylene glycol, dibutyrate GlaxoSmithKline), albutoin, alclofenae, alclometasone ester of triethylene glycol, tributyl phosphate, glycerin, glyc dipropionate, aluminum chlorhydroxyallantoinate (commer erin esters, diacetylglycerin, monoacetylglycerin, glycerol, cially available as ALCOLOXAR) from TRI-K Industries, polyethylene glycol, diethylene glycol, polypropylene gly Inc.), aldecalmycin, aldesleukin, aldioxa, alendronate col, polyglycoldiglycidyl ethers, dimethyl sulfoxide, alky sodium (commercially available as FOSAMAX(R) from lphosphate esters, polycaprolactone, di-2-methoxyethyl Merck), alendronic acid, alentemol, alentemol hydrobro phthalate, dibutyl tartrate, ethyl o-benzoylbenzoate, ethyl mide, aletamine hydrochloride, aleuronium chloride, alexi phthalyl ethyl glycolate, methyl phthalyl ethyl glycolate, dine, alfacalcidol, alfentanil hydrochloride, , alge n-ethyltoluenesulfonamide, o-cresyl p-toluenesulfonate, tri stone acetonide, alglucerase, alliflurane, alinastine, alipamide, methyl phosphate, triethyl phosphate, tributyl phosphate, allantoin, allobarbital, allopurinol, a tachy-kinins (TK) triphenyl phosphate, tripropionin, polycaprolactone, and the antagonist, alonimid, alosetron, alosetron hydrochloride, alo like, any derivative thereof, and any combination thereof. Vudine, alpertine, alpha amylase, alpha idosone, alpidem, 0090. Examples of pigments and dyes may include, but are alprazolam (commercially available as XANAX(R) from not limited to, titanium dioxide, silicon dioxide, tartrazine, Pfizer, Inc.), hydrochloride, alprenoxime hydro E102, phthalocyanine blue, phthalocyanine green, quinacri chloride, alprostadil, alrestatin Sodium, altanserin tartrate, dones, perylene tetracarboxylic acid di-imides, dioxazines, alteplase, althiazide, altretamine, altromycin B. alverinc cit perinones disazo pigments, anthraquinone pigments, carbon rate, alvircept Sudotox, amadinone acetate, amantadine black, metal powders, iron oxide, ultramarine, calcium car hydrochloride, ambamustine, ambomycin, ambruticin, bonate, kaolin clay, aluminum hydroxide, barium Sulfate, ambuphylline, ambuside, amcinafal, amcinonide, amdinocil Zinc oxide, aluminum oxide, CARTASOL(R) dyes (cationic lin, amdinocillin pivoxil, amedalin hydrochloride, amelom dyes, available from Clariant Services) in liquid and/or etaSone, ameltolide, , ametantrone acetate, ameZ granular form (e.g., CARTASOLR) Brilliant Yellow K-6G inium metilsulfate, amfebutamone, amfenac sodium, liquid, CARTASOL(R) Yellow K-4GL liquid, CARTASOL(R) amflutizole, amicycline, mesylate, amidox, US 2014/0113826 A1 Apr. 24, 2014

amifloxacin, amifostine, amikacin, amiloride hydrochloride, beclomethasone dipropionate, befloxatone, beinserazide, aminacrine hydrochloride, aminobenzoate potassium, ami belfosdil, belladonna, beloxamide, bemesetron, bemitradine, nobenzoate Sodium, aminocaproic acid, aminoglutethimide, bemoradan, benapryzine hydrochloride, benazepril hydro aminohippurate Sodium, aminolevulinic acid, aminophylline, chloride, benazeprilat, bendacalol mesylate, bendazac, ben aminorex, aminosalicylate sodium, aminosalicylic acid, droflumethiazide, benflumetol, benidipine, benorterone, amiodarone, amiprilose hydrochloride, amiquinsin hydro benoxaprofen, benoxaprofen, benoximate hydrochloride, chloride, amisulpride, , hydrochloride, benperidol, bentazepam, bentiromide, benurestat, benzbro amlexanoX, amlodipine, amobarbital sodium, amodiaquine, marone, benzethonium chloride, benzetimide hydrochloride, amodiaquine hydrochloride, amorolfine, , amox benzilonium bromide, benzindopyrine hydrochloride, ben icillin, amphecloral, amphetamine Sulfate, amphomycin, Zisoxazole, benzocaine, benzochlorins, hydro amphotericin B, amplicillin, ampiroXicam, ampyZine Sulfate, chloride, benzodepa, benzoidazoxan, benzonatate, benzoyl amduinate, amrinone, aminone, amrubicin, amsacrine, peroxide, benzoylpas calcium, benzoylstaurosporine, ben amythiamicin, anagestone acetate, anagrelide, anakinra. Zquinamide, benzthiazide, benztropine, benztropine mesy ananain, anaritide, anaritide acetate, anastroZole (commer late, benzydamine hydrochloride, benzylpenicilloyl polyl cially available as ARIMIDEXR from AstraZeneca), ana ysine, bepridil, bepridil hydrochloride, beractant, beraprost, Zolene Sodium, ancrod, andrographolide, androstenedione, , berlafenone, bertosamil, berythromycin, besipird angiogenesis inhibitors, angiotensin amide, anidoxime, ine, beta-alethine, betaclamycin B, betamethasone, betami anileridine, anilopam hydrochloride, aniracetam, anirolac, pron, , betaxolol hydrochloride, bethanechol chlo anisotropine methylbromide, anistreplase, anitraZafen, anor ride, bethanidine sulfate, betulinic acid, bevacizumab drin, antagonist D, antagonist G, antarelix, antazoline phos (commercially available as AVASTINR) available from phate, anthelmycin, anthralin, anthramycin, antiandrogen, Genenetech), , bevantolol hydrochloride, bezafi antihemophilic factor (commercially available as XYN brate, bFGF inhibitor, bialamicol hydrochloride, biapenem, THAR) from Pfizer, Inc.), acedapsone, felbamate, antiestro bicalutamide, bicifadine hydrochloride, biclodil hydrochlo gen, antineoplaston, antipyrine, antisense oligonucleotides, ride, bidisomide, , bifonazole, bimakalim, apadoline, apafant, apalcillin Sodium, apaxifylline, apaZone, bimithil, bindarit, biniramycin, binospirone, bioxalomycin aphidicolin glycinate, apixifylline, hydrochlo alpha2, bipenamol hydrochloride, biperiden, biphenamine ride, , apraclonidine hydrochloride, apramycin, hydrochloride, biriperone, bisantrene, bisaramil, bisaziridi aprindine, aprindine hydrochloride, aprosulate Sodium, apro nylspermine, bis-benzimidazole A, bis-benzimidazole B. tinin, maleate, aptiganel, apurinic acid, apurinic bisnafide, bisobrin lactate, , bispyrithione mag acid, aranidipine, aranotin, arbaprostil, arbekicin, 1-methyl sulfex, bistramide D, bistramide K, bistratene A, bithionolate 2-((phenylthio) methyl)-3-carbethoxy-4-(dimethylamino) sodium, besylate, bivalirudin, bizelesin, bleomycin methyl)-5-hydroxy-6-bromindole (commercially available sulfate, bolandiol dipropionate, bolasterone, boldenone as ARBIDOL(R) from Masterlek), hydrochloride, undecylenate, boldine, bolenol, bolmantalate, , arclofenin, ardeparin sodium, (2R,4R)-1-(2S)-5-(diami bosentan, boxidine, brefeldin, breflate, brequinar sodium, nomethylideneamino)-2-((3R)-3-methyl-1,2,3,4-tetrahyd bretazenil, bretylium bosylate, brifentanil hydrochloride, bri roquinolin-8-ylsulfonylaminopentanoyl-4-methyl-piperi monidine, brinolase, brocresine, brocrinat, brofoxine, broma dine-2-carboxylic acid (commercially available as doline maleate, bromazepam, bromchlorenone, bromelains, ARGATROBANR) from GlaxoSmithKline), arginine, bromfenac, brominidione, , bromodiphenhy argipressin tannate, arildone, aripiprazol, , arpi dramine hydrochloride, bromoxamide, bromperidol, bromp nocid, arteflene, artilide fumarate, asimadoline, aspalatone, eridol decanoate, brompheniramine baleate, broperamole, asparaginase, aspartic acid, aspartocin, asperfuran, aspirin, bropirimine, brotizolam, bucamide maleate, . aspoxicillin, asprelin, astemizole, astromicin Sulfate, asula buclizine hydrochloride, bucromarone, budesonide (com crine, atameStane, , atevirdine, , mercially available as RHINOCORTR and ENTOCORTR maleate, atolide, atorvastatin (commercially available as from AstraZeneca), budipine, budotitane, buformin, bumet LIPITOR(R) from Pfizer, Inc.), atosiban, atovaquone, atpenin anide, bunaprolast, , bunolol hydrochloride, bupi B. atracurium besylate, atrimustine, atrinositol, atropine, comide, bupivacaine hydrochloride, buprenorphine hydro auranofin, aureobasidin A, aurothioglucose, avilamycin, chloride, bupropion hydrochloride, buramate, buserelin avoparcin, avridine, nizatidine (commercially available as acetate, hydrochloride, busulfan, butabarbital, AXID(R) from GlaxoSmithKline), axinastatin 1, axinastatin2, butacetin, butaclamol hydrochloride, butalbital, butamben, axinastatin 3, azabon, azacitidinie, azaclorzine hydrochlo butamirate citrate, , butaprost, butedronate tetra ride, azaconazole, azadirachtine, azalanstat dihydrochloride, Sodium, butenafine, buterizine, buthionine Sulfoximine, azaloxan fumarate, azanator maleate, azanidazole, azaper butikacin, butilfenin, butirosin sulfate, butixirate, butixocort one, azaribine, azaserine, aZasetron, azatadine maleate, aza propionate, butoconazole nitrate, butonate, butopamine, thioprine, azathioprine sodium, azatoxin, azatyrosine, azelaic butoprozine hydrochloride, butorphanol, butoxamine hydro acid, azelastine, azelnidipine, azepindole, azetepa, azimilide, chloride, hydrochloride, cactinomycin, cadex azithromycin, azlocillin, azolimine, aZosemide, azotomycin, omer iodine, caffeine, calanolide A, calcifediol, calcipot aztreonam, aZumolene Sodium, bacampicillin hydrochloride, riene, calcipotriol, calcitonin, calcitriol, calcium baccatin III, bacitracin, baclofen, bacoside A, bacoside B, undecylenate, callphostin C, calusterone, cambendazole, bactobolamine, balanol, balaZipone, balhimycin, balofloxa camonagrel, camptothecin derivatives, canarypox IL-2, can cin, balsalazide, bambermycins, , bamethan Sul desartan, candicidin, candoXatril, candoxatrilat, caniglibose, fate, bamifylline hydrochloride, bamidazole, baohuoside 1, canrenoate potassium, canrenone, capecitabine, capobenate barmastine, barnidipine, basifungin, batanopride hydrochlo Sodium, capobenic acid, capreomycin Sulfate, capromab, ride, batebulast, batelapine maleate, batimastat, beauvericin, capsaicin, captopril, capuride, caracemide, carbachol, carba becanthone hydrochloride, becaplermin, becliconazole, dox, carbamazepine, carbamide peroxide, carbantel lauryl US 2014/0113826 A1 Apr. 24, 2014

Sulfate, carbaspirin calcium, carbazeran, carbazomycin C, phosphate, clogestone acetate, clomacran phosphate, clom carbenicillin potassium, carbenoXolone sodium, carbetimer, egestone acetate, clometherone, clomethiazole, clomifene carbetocin, carbidopa, carbidopa-levodopa, carbinoxamine analogues, clominorex, clomiphene, hydro maleate, carbiphene hydrochloride, carbocloral, carbocys chloride, clonazepam, , clonitrate, clonixeril, teine, carbol-fuchsin, carboplatin, carboprost, carbovir, car clonixin, clopamide, , cloperidone hydrochlo boxamide-amino-triazole, carboxyamidotriazole, carboxym ride, clopidogrel (commercially available as PLAVIX(R) from ethylated beta-1,3-glucan, hydrochloride, CaRest Bristol-Myers Squibb and Sanofi Pharmaceuticals), clopi M3, carfentanil citrate, carisoprodol, carmantadine, carmus mozide, clopipazan mesylate, clopirac, cloprednol, clopros tine, CARN 700, camidazole, caroxazone, carperitide, car tenol sodium, cloraZepate dipotassium, clorethate, clorex phenazine maleate, carprofen, carsatirin Succinate, carta olone, cloroperone hydrochloride, clorprenaline Zolate, , carteolol hydrochloride, cartilage derived hydrochloride, clorsulon, clortermine hydrochloride, closan inhibitor, carubicin hydrochloride, carumonam Sodium, tel, closiramine aceturate, clothiapine, clothixamide maleate , carvotroline, carvotroline hydrochloride, carze cloticaSone propionate, clotrimazole, cloxacillin benzathine, lesin, casein kinase inhibitors (ICOS), castanospermine, cau cloxyquin, , cocaine, coccidioidin, codeine, rumonam, cebaracetam, cecropin B, cedefingol, cefaclor, codoxime, colchicine, colestimide, colestipol hydrochloride, cefadroxil, cefamandole, cefaparole, cefatrizine, cefazaflur colestolone, colforsin, colfosceril palmitate, colistimethate Sodium, cefazolin, cefbuperaZone, cefcapene pivoxil, cefdal Sodium, colistin Sulfate, collismycin A, collismycin B, col oxime pentexil tosilate, cefdinir, cefditoren pivoxil, terol mesylate, combretastatin A4, combretastatin analogue, cefepime, cefetamet, cefetecol, cefixime, cefluprenam, complestatin, conagenin, conorphone hydrochloride, conti cefinenoXime hydrochloride, cefinetazole, cefiminlox, cefo gnasterol, contortrostatin, cormethasone acetate, corticorelin dizime, cefonicid sodium, cefoperaZone sodium, ceforanide, ovine triflutate, corticotropin, cortisone acetate, cortivaZol. cefoselis, cefotaxime Sodium, cefotetan, cefotiam, cefoxitin, cortodoxone, cosalane, costatolide, cosyntropin, cotinine, cefoZopran, cefpimizole, cefpiramide, cefpirome, cefpo warfarin (commercially available as COUMADINR) from doXime proxetil, cefprozil, cefroxadine, cefsulodin, ceftazi Bristol-Myers Squibb), coumermycin, crambescidin 816, dime, cefteram, ceftibuten, ceftizoxime Sodium, ceftriaxone, crilvastatin, crisinatol, cromitrile Sodium, cromolyn Sodium, cefuroxime, celastrol, celikalim, , cepacidine A, crotamiton, cryptophycin 8, cucumariosid, cuprimyxin, cura cephacetrile Sodium, cephalexin, cephaloglycin, cephalori cin A, curdlan Sulfate, Zinc hyaluran (commercially available dine, cephalothin Sodium, cephapirin Sodium, cephradine, as CURIOSINR) from Gedeon Richter), cyclacillin, cyclazo cericlamine, cerivastatin, ceronapril, certoparin sodium, cine, cyclazosin, cyclic HPMPC, cyclindole, cycliramine ceruletide, cetaben Sodium, cetalkonium chloride, maleate, cyclizine, cyclobendazole, , hydrochloride, cetiedil, cetirizine, cetophenicol, cetraxate cyclobut A, cyclobut G, cyclocapron, cycloguanil pamoate, hydrochloride, cetrorelix, cetuximab (commercially avail cycloheximide, cyclopentanthraquinones, cyclopenthiazide, able as ERBITUXOR) from Eli Lilly and Company), cetylpy cyclopentolate hydrochloride, cyclophenazine hydrochlo ridinium chloride, chenodiol, chlophedianol hydrochloride, ride, cyclophosphamide, cycloplatam, cyclopropane, cyclos chloral betaine, chlorambucil, chloramphenicol, chlordan erine, cyclosin, cyclosporine, cyclothialidine, cyclothiazide, toin, chlordiazepoxide, chlorhexidine gluconate, chlorins, cyclothiazomycin, cyheptamide, cypemycin, cypenamine chlormadinone acetate, chloroorienticin A, chloroprocaine hydrochloride, cyprazepam, hydrochloride, hydrochloride, chloropropamide, chloroquine, chloroqui cyprolidol hydrochloride, cyproterone, cyproximide, cys noxaline Sulfonamide, chlorothiazide, chlorotrianisene, teamine, cysteine hydrochloride, cystine, cytarabine, cytara chloroxine, chloroxylenol, chlorphenesin carbamate, chlor bine hydrochloride, cytarabine ocfosfate, cytochalasin B, pheniramine maleate, , chlorpropamide, cytolytic factor, cytostatin, dacarbazine, dacliximab, dactimi , chlortetracycline bisulfate, chlorthalidone, cin, dactinomycin, daidzein, daledalin tosylate, dalfopristin, chlorZoxazone, cholestyramine resin, chromonar hydrochlo dalteparin Sodium, daltroban, dalvastatin, danaparoid, dana ride, cibenzoline, cicaprost, hydrochloride, Zol, dantrolene, daphlnodorin A, , dapitant, ciclazindol, ciclesonide, cicletanine, ciclopiroX, cicloprofen, dapoxetine hydrochloride, dapsone, daptomycin, dargilita , cidofovir, hydrochloride, cifenline, Zone sodium, darifenacin, darlucin A, darodipine, darsidom ciglitaZone, ciladopa hydrochloride, cilansetron, cilastatin ine, darusentan, daunorubicin hydrochloride, daZadrol male Sodium, cilaZapril, cilnidipine, mesylate, cilobra ate, dazepinil hydrochloride, daZmegrel, dazopride fumarate, dine, cillofungin, cilostazol, , cimetidine, dazoxiben hydrochloride, debrisoquin sulfate, decitabine, cimetropium bromide, cinalukast, cinanserin hydrochloride, deferiprone, deflazacort, dehydrocholic acid, dehydrodidem cinepazet maleate, cinflumide, cingestol, cinitapride, cin nin B, dehydroepiandrosterone, delapril, delapril hydrochlo namedrine, cinnarizine, cinolazepam, cinoxacin, cinperene, ride, delavirdine mesylate, deleguamine, delfaprazine, del cinromide, cintaZone, cintriamide, cioteronel, cipamfylline, madinone acetate, delmopinol, delphinidin, demecarium ciprefadol Succinate, ciprocinonide, ciprofibrate, ciprofloxa bromide, demeclocycline, demecycline, demoxepam, deno cin, ciprostene, ciramadol, cirolemycin, cisapride, cisatracu fungin, deoxypyridinoline, 2-propylpentanoic acid (commer rium besilate, cisconazole, cisplatin, cis-porphyrin, cistineX cially available as DEPAKOTE(R) from Abbott), deprodone, ine, citalopram, citenamide, citicoline, citreamicin alpha, deprostil, depsidomycin, deramciclane, dermatan Sulfate, cladribine, clamoxyquin hydrochloride, clarithromycin, desciclovir, descinolone acetonide, desflurane, clausenamide, clavulanate potassium, claZolam, claZolimine, hydrochloride, desirudin, deslanoside, deslorelin, desmo clebopride, clemastine, Clentiazem maleate, clidinium bro pressin, desogestrel, desonide, desoximetasone, desoxoami mide, clinafloxacin, clindamycin, clioquinol, clioxamide, odarone, desoxycorticosterone acetate, detajmium bitartrate, cliprofen, clobazam, clobetasol propionate, clobetaSone hydrochloride, detirelix acetate, devazepide, dex butyrate, clocortolone acetate, clodanolene, clodazon hydro amethasone, dexamisole, dexbrompheniramine maleate, chloride, clodronic acid, clof azimine, clofibrate, clofilium dexchlorpheniramine maleate, dexclamol hydrochloride, US 2014/0113826 A1 Apr. 24, 2014

dexetimide, dexfenfluramine hydrochloride, dexifosfamide, mesylates, ergonovine maleate, tartrate, deximafen, dexivacaine, dexketoprofen, dexloxiglumide, , ersofermin, erythritol, erythrity1 tetranitrate, , dexormaplatin, dexoxadrol hydrochlo erythromycin, esmolol hydrochloride, esomeprazole (com ride, dexpanthenol, dexpemedolac, dexpropranolol hydro mercially available as NEXIUM(R) from AstraZeneca), eso chloride, dexraZoxane, dexSotalol, dextrin 2-sulphate, dex rubicin hydrochloride, esproquin hydrochloride, estaZolam, troamphetamine, dextromethorphan, dextrorphan estradiol, estramustine, estramustine analogue, estraZinol hydrochloride, dextrothyroxine Sodium, dexVerapamil, deza hydrobromide, estriol, estrofurate, estrogen agonists, estro guanine, dezinamide, dezocine, hydrochloride, gen antagonists, estrogens, conjugated estrogens, esterified, diamocaine cyclamate, diapamide, diatrizoate meglumine, estrone, estropipate, esuprone, hydrochloride, diatrizoic acid, diaveridine, diazepam, diaziquone, diaZOX etanidazole, etanterol, etarotene, etazolate hydrochloride, ide, dibenzepin hydrochloride, dibenzothiophene, dibucaine, eterobarb, ethacizin, ethacrynate Sodium, ethacrynic acid, dichliorvos, dichloralphenaZone, dichlorphenamide, dicir ethambutol hydrochloride, ethamivan, ethanolamine oleate, enone, diclofenac sodium, dicloxacillin, dicranin, dicumarol, ethehlorvynol, ether, ethinyl estradiol, ethiodized oil, dicyclomine hydrochloride, didanosine, didemnin B, didox, ethionamide, ethonam nitrate, ethopropazine hydrochloride, dienestrol, dienogest, diethylcarbamazine citrate, diethylho ethosuximide, ethotoin, ethoxazene hydrochloride, ethyben mospermine, diethylnorspermine, diethylpropion hydrochlo Ztropine, ethyl chloride, ethyl dibunate, ethylestrenol, ethyn ride, diethylstilbestrol, difenoximide hydrochloride, diol, ethynerone, ethynodiol diacetate, etibendazole, eti difenoxin, diflorasone diacetate, difloxacin hydrochloride, docaine, etidronate disodium, etidronic acid, etifenin, difluanine hydrochloride, diflucortolone, diflumidone etintidine hydrochloride, etizolam, etodolac, etofenamate, Sodium, diflunisal, difluprednate, diftalone, digitalis, digi etoformin hydrochloride, etomidate, etonogestrel, etoperi toxin, digoxin, dihexyverine hydrochloride, dihydrexidine, done hydrochloride, etoposide, etoprine, etoxadrol hydro dihydro-5-azacytidine, dihydrocodeine bitartrate, dihydroer chloride, etoZolin, etrabamine, etretinate, etryptamine gotamine mesylate, hihydroestosterone, dihydrostreptomy acetate, eucatropine hydrochloride, eugenol, euprocin hydro cin Sulfate, dihydrotachysterol, dihydrotaxol, phenytoin chloride, eveninomicin, exametazine, examorelin, (commercially available as DILANTINR) from Parke, Davis hydrochloride, exemestane, exetimibe (commercially avail & Company), dilevalol hydrochloride, diltiazem hydrochlo able as ZETIAR) from Merck), fadrozole, faerieflungin, fam ride, dimefadane, dimefline hydrochloride, dimenhydrinate, ciclovir, famotidine (commercially available as PEPCIDR) dimercaprol, dimethadione, dimethindene maleate, dimethis from Merck), fampiridine, fantofarone, fantridone hydrochlo terone, dimethyl prostaglandin A1, dimethylsulfoxide, dim ride, faropenem, fasidotril, fasudil, fazarabine, fedotozine, ethylhomospermine, dimiracetam, dimoxamine hydrochlo felbamate, felbinac, felodipine, fely pressin, femalamide, fen ride, dinoprost, dinoprostone, dioxadrol hydrochloride, amole, fenbendazole, fenbufen, fencibutirol, fenclofenac, dioxamycin, diphenhydramine citrate, diphenidol, diphe fenclonine, fenclorac, fendosal, fenestrel, fenethylline hydro noxylate hydrochloride, diphenyl spiromustine, diplivefin chloride, fenfluramine hydrochloride, fengabine, fenimide, hydrochloride, diplivefrin, dipliency prone, , fenisorex, hydrochloride, fenmetramide, dipropylnorspermine, dipyridamole, dipyrithione, dipyrone, fenobam, fenoctimine sulfate, fenofibrate, fenoldopam, feno dirithromycin, discodermolide, disobutamide, disofenin, dis profen, , fenpipalone, fenprinast hydrochloride, fen opyramide, disoxaril, disulfuram, ditekiren, divalproex prostalene, fenguizone, fenretinide, , fentanyl cit Sodium, dizocilpine maleate, , docarpamine, rate, fentiazac, fenticlor, fenticonazole, fenyripol docebenone, docetaxel, doconazole, docosanol, dolfetilide, hydrochloride, fepradinol, ferpifosate sodium, ferristene, fer dolasetron, drotrecogin alfa (commercially available as rixan, ferrous Sulfate, ferumoxides, ferumoxsil, fetoxylate XIGRIS(R) from Eli Lilly and Company), dulloxetine hydro hydrochloride, fexofenadine, fezolamine fumarate, fiacitab chloride (commercially available as CYMBALTAR) from Eli ine, fialuridine, fibrinogen I 125, filgrastim, filipin, finasteride Lilly and Company), ebastine, ebiratide, ebrotidine, ebselen, (commercially available as PROPECIAR) from Merck), fla ecabapide, ecabet, ecadotril, ecdlisteron, echicetin, echistatin, vodilol maleate, flavopiridol, flavoxate hydrochloride, flaza echothiophate iodide, eclanamine maleate, eclaZolast, eco lone, flecainide, flerobuterol, fleroxacin, flesinoxan, mustine, econazole, ecteinascidin 722, edaravone, edatrex sulfate, fletazepam, flezelastine, flobufen, floctafenine, flo ate, edelfosine, edifolone acetate, edobacomab, edoxudine, moxef, flordipine, florfenicol, florifenine, flosatidil, flose edrecolomab, edrophonium chloride, edroxyprogesteone quinan, floxacillin, floXuridine, fluasterone, fluazacort, fluba acetate, efegatran, eflornithine, efonidipine, egualcen, elant nilate hydrochloride, flubendazole, flucindole, flucloronide, rine, eleatonin, elemene, eletriptan, elgodipine, eliprodil, fluconazole, flucytosine, fludalanine, fludarabine phosphate, elsamitrucin, eltenae, elucaine, emalkalim, emedastine, fludazonium chloride, fludeoxyglucose F 18, fludorex, emetine hydrochloride, emiglitate, emilium tosylate, emite fludrocortisone acetate, flufenamic acid, flufenisal, flumaze fur, emoctakin, enadoline hydrochloride, enalapril, enalapri nil, flumecinol, flumequine, flumeridone, flumethasone, flu lat, enalkiren, enaZadrem, encyprate, endralazine mesylate, metramide, flumeZapine, fluminorex, flumizole, flumox endrysone, enflurane, englitaZone, enilconazole, enisoprost, onide, flunarizine, flunidazole, flunisolide, flunitrazepam, enlimomab, enloplatin, enofelast, enolicam sodium, enoxa flunixin, fluocalcitriol, fluocinolone acetonide, fluocinonide, cin, enoxacin, enoxaparin Sodium, enoxaparin Sodium, fluocortin butyl, fluocortolone, fluorescein, fluorodaunoruni enoXimone, enpiroline phosphate, enprofylline, empromate, cin hydrochloride, fluorodopa F 18, fluoroformylone, fluoro entacapone, enterostatin, enviradene, enviroXime, , quinolones, fluorometholone, fluorouracil, hydro epicillin, epimestrol, epinephrine, epinephrylborate, epipro chloride, fluoxetine, fluoxymesterone, , pidine, epirizole, epirubicin, epitetracycline hydrochloride, fluperamide, fluperolone acetate, decanoate, epithiazide, epoetinalfa, epoetin beta, epoprostenol, epopros flupirtine, fluprednisolone, fluproduaZone, fluprostenol tenol sodium, epoxymeXrenone, epristeride, eprosartan, Sodium, fluquaZone, fluradoline hydrochloride, flurandreno eptastigmine, equilenin, equilin, erbuloZole, erdosteine, lide, flurazepam hydrochloride, flurbiprofen, fluretofen, flu US 2014/0113826 A1 Apr. 24, 2014 rithromycin, fluorocitabine, fluorof amide, fluorogestone chloride, imidoline hydrochloride, imidurea, imiloxanhydro acetate, flurothyl, fluoroxene, fluspiperone, fluspirilene, flu chloride, imipenem, hydrochloride, imiquimod, ticasone propionate (commercially available as ADVAIRR immunostimulant peptides, impromidine hydrochloride, from GlaxoSmithKline), fluticasone furoate, flutrimazole, indacrinone, indapamide, indecainide hydrochloride, indel flutroline, fluvastatin, fluvastatin sodium, fluvoxamine, fluzi oxazine hydrochloride, indigotindisulfonate sodium, indi namide, folic acid, follicle regulatory protein, folliculostatin, navir, indocyanine green, indolapril hydrochloride, indol fomepizole, fonazine mesylate, forasartan, forfenimex, for idan, indometacin, indomethacin Sodium, indoprofen, fenirmex, formestane, formocortal, , fosarilate, , indorenate hydrochloride, indoxole, indriline fosazepam, foscarnet Sodium, fosfomycin, foSfonet Sodium, hydrochloride, infliximab (commercially available as REMI fosinopril, fosinoprilat, fosphenyloin, fosquidone, fostedil, CADE(R) from Janssen Biotech, Inc.), inocoterone, inogatran, fostriecin, fotemustine, fuchsin, basic, fumoxicillin, fungi inolimomab, inositol niacinate, insulin, insulin glargine mycin, furaprofen, furazolidone, furazolium chloride, fure (commercially available as LANTUSR) from Sanofi-Aven grelate sodium, furobufen, furodazole, furosemide, fusidate tis), interferons, interferon beta-1a (commercially available Sodium, fusidic acid, gabapentin, gadobenate dimeglumine, as AVONEX(R) from BIOGEN), interleukins, intrazole, gadobenic acid, gadobutrol, gadodiamide, gadolinium texa hydrochloride, iobenguane, iobenzamic acid, phyrin, gadopentetate dimeglumine, gadoteric acid, gadoteri iobitridol, iocarmate meglumine, iocarmic acid, iocetamic dol, gadoversetamide, galantamine, galdansetron, acid, iodamide, iodine, iodipamide meglumine, iodixanol, galdansetron hydrochloride, gallamine triethiodide, gallium iodoamiloride, iodoantipyrine I 131, iodocholesterol I 131, nitrate, gallopamil, galocitabine, gamfexine, gamolenic acid, iododoxorubicin, iodohippurate sodium I 131, iodopyracet I ganciclovir, ganirelix, ganirelix acetate, gelatinase inhibitors, 125, iodoquinol, iodoxamate meglumine, iodoxamie acid, gemcadiol, gemcitabine (commercially available as ioglicic acid, iofetamine hydrochloride I 123, iofratol, ioglu GEMZARR) from Eli Lilly and Company), gemeprost, gem col, ioglucomide, ioglycamic acid, iogulamide, iohexyl, fibrozil, gentamicin Sulfate, gentian violet, , gesta iomeprol, iomethin I 125, iopamidol, iopanoic acid, iopentol, clone, gestodene, gestonorone caproate, gestrinone, geVotro iophendylate, ioprocemic acid, iopromide, iopronic acid, line hydrochloride, girisopam, glaspimod, glaucocalyxin A, iopydol, iopydone, iopyrol, iosefamic acid, ioseric acid, ioSu glemanserin, gliamilide, glibornuride, glicetanile Sodium, lamide meglumine, ioSumetic acid, iotasul, iotetric acid, gliflumide, glimepiride, glipizide, gloximonam, glucagon, iothalamate Sodium, iothalamic acid, iotriside, iotrolan, glutapyrone, glutathione inhibitors, glutethimide, glyburide, iotroXic acid, iotyrosine I 131, ioversol, ioxagiate Sodium, glycopine, glycopril, glycopyrrolate, glyhexamide, glymi ioxaglate meglumine, ioxaglic acid, ioXilan, ioxotrizoic acid, dine sodium, glyoctamide, glyparamide, colloidal gold Au ipazilide, ipenoxazone, ipidacrine, ipodate calcium, 198, gonadoctrinins, gonadorelin, gonadotropins, goserelin, ipomeanol, 4-, ipratropium bromide, ipriflavone, iprindole, gramicidin, granisetron, grepafloxacin, griseofulvin, guaiap iprofenin, ipronidazole, iproplatin, iproxamine hydrochlo ate, guaithylline, , guanabenz acetate, guanadrel ride, , irbesartan, irinotecan, irloxacin, iroplact, Sulfate, guancydine, monosulfate, irsogladine, irtemazole, isalsteine, isamoxole, isbogrel, hydrochloride, guanisoquin Sulfate, guanoclor Sulfate, gua isepamicin, isobengaZole, isobutamben, isocarboxazid, iso noctine hydrochloride, , guanoxan Sulfate, gua conazole, isoetharine, isofloxythepin, isoflupredone acetate, noxyfen Sulfate, gusperimus trihydrochloride, halazepam, isoflurane, isofluorophate, isohomohalicondrin B, isoleucine, halcinonide, halichondrin B, halobetasol propionate, halof isomazole hydrochloride, isomylamine hydrochloride, iso antrine, halofantrine hydrochloride, halofenate, halofugi niazid, isopropamide iodide, isopropyl alcohol, isopropyl none hydrobromide, halomon, galopemide, galoperidol. unoprostone, isoproterenolhydrochloride, isosorbide, isosor halopredone, haloprogesterone, haloprogin, halothane, bide mononitrate, isotiquimide, isotretinoin, isoxepac, isoxi halquinols, hamycin, han menopausal gonadotropins, cam, hydrochloride, isradipine, itameline, hatomamicin, hatomarubigin A, hatomarubigin B, hatomaru itasetron, itaZigrel, itopride, itraconazole, ivermectin, jas bigin C, hatomarubigin D, heparin Sodium, hepsulfam, plakinolide, josamycin, kahalalide F. kalafungin, kanamycin heregulin, hetacillin, heteronium bromide, hexachlorophene: Sulfate, ketamine hydrochloride, , ketazocine, hydrogen peroxide, hexafluorenium bromide, hexamethylene ketazolam, kethoxal, ketipramine fumarate, ketoconazole, bisacetamide, hexedine, hexobendine, Sulfate, ketoprofen, ketorfanol, ketorolac, ketotifen fumarate, kitasa hexylresorcinol, histamine phosphate, histidine, histoplas mycin, hydrochloride, lacidipine, lacidipine, lacti min, histrelin, homatropine hydrobromide, hoquizil hydro tol, lactivicin, laennec, lafutidine, lamellarin-n triacetate, chloride, human chorionic gonadotropin, hycanthone, lamifiban, lamivudine, lamotrigine, lanoconazole, LAN hydralazine hydrochloride, hydralazine polistirex, hydro OXINR) (digoxin, available from GlaxoSmithKline), lan chlorothiazide, hydrocodone bitartrate, hydrocortisone, perisone, lanreotide, lanSoprazole (commercially available as hydroflumethiazide, hydromorphone hydrochloride, PREVAID(R) from Takeda Pharmaceuticals, Inc.), latano hydroxyamphetamine hydrobromide, hydroxychloroquine prost, lateritin, laurocapram, lauryl isoquinolinium bromide, Sulfate, hydroxyphenamate, hydroxyprogesterone caproate, lavoltidine Succinate, lazabemide, lecimibide, leinamycin, hydroxyurca, hydroxy Zine hydrochloride, hymecromone, lemildipine, leminoprazole, lenercept, leniquinsin, hyoscyamine, hypericin, ibafloxacin, ibandronic acid, lenograstim, lenperone, lentinan Sulfate, leptin, leptolstatin, ibogaine, ibopamine, ibudilast, ibufenac, ibuprofen, ibutilide lercanidipine, lergotrile, lerisetron, letimide hydrochloride, fumarate, icatibant acetate, ichthammol, icotidine, idarubi letraZuril, letrozole, leucine, leucomyzin, leuprolide acetate, cin, idoxifene, idoxuridine, idramantone, iemefloxacin, ieso leuprolide, leuprorelin, levamfetamine Succinate, levamisole, pitron, ifetroban, ifosfamide, ilepeimide, illimaquinone, levdobutamine lactobionate, levcromakalim, levetiracetam, ilmofosine, illomastat, illonidap, illoperidone, iloprost, imafen , , levobupivacaine, levocabastine, hydrochloride, imaZodan hydrochloride, imidapril, imidaze levocarnitine, levodopa, levodropropizine, levofloxacin nil, imidazoacridones, imidecyl iodine, imidocarb hydro (commercially available as LEVAQUINR) from Jessen Phar US 2014/0113826 A1 Apr. 24, 2014

maceuticals, Inc.), levofluraltadone, levoleucovorin calcium, hydrochloride, methocarbamol, methohexital sodium, levomethadyl acetate, levomethadyl acetate hydrochloride, methopholine, methotrexate, methotrimeprazine, meth , levonantradol hydrochloride, levonordefrin, Oxatone, methoxyflurane, methSuximide, methyclothiazide, levonorgestrel, levopropoxyphene napsylate, levopropylcil methyl 10 palmoxirate, methylatropine nitrate, methylbenze lin potassium, levormeloxifene, levorphanol tartrate, levosi thonium chloride, , methyldopate hydrochloride, mendan, levoSulpiride, levothyroxine Sodium, levoxadrol methylene blue, methylergonovine maleate, methylhista hydrochloride, lexipa?ant, lexithromycin, liarozole, libenza mine, R-alpha, methylinosine monophosphate, methylpheni pril, lidamidine hydrochloride, lidocaine, lidofenin, lidofla date hydrochloride, methylprednisolone, methyltestosterone, zine, lifarizine, lifibrate, lifibrol, linarotene, lincomycin, lin methynodiol diacelate, , methysergide maleate, ear polyamine analogue, linogliride, linopirdine, linotroban, metiamide, metiapine, metioprim, metipamide, metipra linsidomine, lintitript, lintopride, liothyronine I 125, liothy nolol, metizoline hydrochloride, metkephamidacetate, meto ronine Sodium, liotrix, lirexapride, lisinopril, lissoclinamide clopramide, metocurine iodide, metogest, metolaZone, 7, lixazinone sulfate, lobaplatin, lobenzarit sodium, lobu metopimazine, metoprine, , metoquizine, metri cavir, lodelaben, lodoxamide, lofemizole hydrochloride, fonate, metrizamide, metrizoate Sodium, metronidazole, lofentanil oxalate, hydrochloride, meturedepa, metyrapone, metyrosine, mexiletine hydrochlo hydrochloride, lombricine, lomefloxacin, lomerizine, lom ride, mexrenoate potassium, meZlocillin, mfonelic acid, etraline hydrochloride, lometrexol, lomitapide, lomofungin, hydrochloride, mibefradil, mibefradil dihydro lornoxicam, lomustine, lonapalene, lonazolac, lonidamine, chloride, mibolerone, michellamine B, miconazole, micro loperamide hydrochloride, loracarbef, lorajmine hydrochlo colin A, midaflur, midazolam hydrochloride, , ride, loratadine, lorazepam, lorbamate, lorcainide hydrochlo mifepristone, mifobate, miglitol, millacemide, milameline, ride, lorecleZole, lorglumide, lormetazepam, lornoxicam, lor mildronate, milemperone, millipertine, milnacipran, mil noxicam, lortalamine, lorZafone, losartan (commercially rinone, miltefosine, mimbane hydrochloride, minaprine, available as COZAAR(R) from Merck), losigamone, losox minaxolone, minocromil, minocycline, minoxidil, miofla antrone, losulazine hydrochloride, loteprednol, lovastatin, Zine hydrochloride, miokamycin, mipragoside, mirfentanil, loviride, , loxoribine, lubeluzole, lucanthone hydro mirimoStim, mirincamycin hydrochloride, mirisetron male chloride, lufironil, lurosetron mesylate, lurtotecan, luteiniz ate, , mismatched double stranded RNA, mis ing hormone, lutetium, lutrelin acetate, luzindole, lyapolate onidazole, misoprostol, mitindomide, mitocarcin, mitocro Sodium, lycetamine, lydicamycin, lydimycin, lynestrenol, min, mitogillin, mitoguaZone, mitolactol, mitomalcin, lypressin, lysine, lysofylline, lysostaphin, lytic peptides, mitomycin, mitonafide, mitosper, mitotane, mitoxantrone, maduramicin, mafenide, magainin 2 amide, magnesium sali mivacurium chloride, mivaZerol, mixanpril, mixidine, mizo cylate, magnesium sulfate, magnolol, maitansine, male lastine, mizoribine, moclobemide, modafinil, modaline Sul thamer, mallotochromene, mallotojaponin, malotilate, man fate, modecamide, moexipril, mofarotene, mofegiline hydro gafodipir, manidipine, maniwamycin A, mannitol, chloride, mofeZolac, molgramoStim, molinaZone, molindone mannostatin A, manumycin E, manumycin F, MAPK/ERK hydrochloride, molsidomine, mometasone, male kinase (MEK) inhibitors, mapinastine, , marim ate, monensin, monoctanoin, montelukast sodium (commer astat, masoprocol, maspin, massetolide, matrilysin inhibitors, cially available as SINGULAIRR) available from Merck), maytansine, mazapertine Succiniate, mazindol, mebenda montirelin, mopidamol, moracizine, morantel tartrate, mori Zole, mebeverine hydrochloride, mebrofenin, mebutamate, cizine, morniflumate, morphine, morphine Sulfate, morrhuate mecamylamine hydrochloride, mechlorethamine hydrochlo Sodium, , mosapride, motilide, motretinide, ride, meclocycline, meclofenamate Sodium, mecloqualone, moxalactam disodium, moxazocine, moxiraprine, moxnida meclorisone dibutyrate, medazepam hydrochloride, Zole, moXonidine, mumps skin testantigen, mustard antican medorinone, medrogestone, , medroxyprogester cer agent, muZolimine, mycaperoxide B, mycophenolic acid, one (commercially available as DEPO-PROVERAR) from myriaporone, nabazenil, nabilone, nabitan hydrochloride, Pfizer, Inc.), medrysone, meelizine hydrochloride, mefe naboctate hydrochloride, nabumetone, n-acetyldinaline, namic acid, mefenidil, mefenorex hydrochloride, mefexam nadide, nadifloxacin, , nadroparin calcium, nafadot ide, mefloquine hydrochloride, mefruside, megalomicin ride, nafamo.stat, nafarelin, nafcillin sodium, nafenopin, potassium phosphate, megestrol acetate, meglumine, meglu nafimidone hydrochloride, naflocort, nafomine malate, tol, melengestrol acetate, hydrochloride, mel nafoxidine hydrochloride, nafronyl oxalate, naftifine hydro phalan, memotine hydrochloride, menabitan hydrochloride, chloride, , naglivan, nagreStip, nalbuphine hydro menoctone, menogaril, menotropins, meobentine Sulfate, chloride, nalidixate Sodium, nalidixic acid, nalmefene, mepartricin, mepenZolate bromide, meperidine hydrochlo nalmexone hydrochloride, naloxone/pentazocine, naltrex ride, mephentermine Sulfate, mephenyloin, mephobarbital, one, namoxyrate, nandrolone phenpropionate, nantradol mepivacaine hydrochloride, meprobamate, meptazinol hydrochloride, napactadine hydrochloride, napadisilate, hydrochloride, medulidox, meralein sodium, merbarone, mer napamezole hydrochloride, napavin, hydro captopurine, mercufenol chloride, mercury, meropenem, chloride, naphterpin, naproxen, naproXol, napsagatran, nara mesalamine, meseclaZone, , mesterolone, nol hydrochloride, narasin, naratriptan, nartograstim, nasaru mestranol, meSuprine hydrochloride, metalol hydrochloride, plase, natamycin, nateplase, naxagolide hydrochloride, metaproterenol polistirex, bitartrate, metaxa , nebramycin, medaplatin, nedocromil, lone, meteneprost, meterelin, metformin, methacholine chlo hydrochloride, neflumozide hydrochloride, nefopam hydro ride, methacycline, methadone hydrochloride, methadyl chloride, neleZaprine maleate, nemazoline hydrochloride, acetate, methalthiazide, methamphetamine hydrochloride, nemorubicin, neomycin palmitate, neostigmine bromide, methaqualone, methazolamide, methdilazine, methenamine, neridronic acid, netilmicin Sulfate, neutral endopeptidase, methenolone acetate, methetoin, methicillin Sodium, methi neutramycin, nevirapine, nexeridine hydrochloride, niacin, mazole, methioninase, methionine, methisaZone, methixene nibroxane, nicardipine hydrochloride, , niclosa US 2014/0113826 A1 Apr. 24, 2014 mide, nicorandil, nicotinyl alcohol, nicotine (commercially pemirolast, pemoline, penamecillin, sulfate, pen available as NICOTROL(R) NS from Pfizer, Inc.), nifedipine, ciclovir, penfluridol, penicillin G benzathine, penicillin G nifirmerone, nifluridide, nifuradene, nifuraldezone, nifuratel, potassium, penicillin G procaine, penicillin G Sodium, peni nifuratrone, nifurdazil, nifurimide, nifurpirinol, cillin V, penicillin V benzathine, penicillin V hydrabamine, nifurquinazol, nifurthiazole, nilutamide, nilvadipine, nima penicillin V potassium, pentabamate, pentaerythritol tetrani Zone, nimodipine, niperotidine, niravoline, niridazole, nisa trate, pentafuside, pentamidine, pentamorphone, bentamus mycin, nisbuterol mesylate, nisin, nisobamate, nisoldipine, tine, pentapiperium methylsulfate, pentazocine, pentetic nisoxetine, nisterime acetate, nitarSone, nitazoxamide, nite acid, pentiapine maleate, pentigetide, pentisomicin, pentizi capone, nitrafudam hydrochloride, nitralamine hydrochlo done sodium, pentobarbital, pentomone, pentopril, pentosan, ride, nitramisole hydrochloride, nitrazepam, nitrendipine, pentostatin, pentoxifylline, pentrinitrol, pentroZole, peplo nitrocycline, nitrodan, nitrofurantoin, nitrofuraZone, nitro mycin Sulfate, pepstatin, perflubron, perfof amide, perfosfa glycerin, nitromersol, nitromide, nitromifene citrate, nitrous mide, , perhexyline maleate, perillyl alcohol, perin oxide, nitroxide antioxidant, nitrullyn, nivaZol. nivimedone dopril, perindoprilat, , permethrin, , Sodium, nizatidine, noberastine, nocodazole, nogalamycin, , phenacemide, phenaridine, phenazinomycin, nolinium bromide, nomifensine maleate, noracymethadol phenaZopyridine hydrochloride, phenbutaZone sodium glyc hydrochloride, norbolethone, norepinephrinebitartrate, nore erate, phencarbamide, phencyclidine hydrochloride, phen thindrone, norethynodrel, norfloxacin, norflurane, norgesti dimetrazine tartrate, phenelZine Sulfate, phenmetrazine mate, norgestomet, norgestrel, hydrochloride, hydrochloride, phenobarbital, hydro noscapine, novobiocin Sodium, N-Substituted benzaimides, chloride, phenprocoumon, phenserine, phensuccinal, phen nufenoXole, nylestriol, nystatin, O6-benzylguanine, obi Suximide, phentermine, phentermine hydrochloride, phento doXime chloride, , ocfentanil hydrochloride, oci lamine mesilate, phentoxifylline, phenyl aminosalicylate, naplon, octanoic acid, octaZamide, octenidine hydrochloride, phenylacetate, phenylalanine, phenylalanyl ketoconazole, octodrine, octreotide, phosphate, ofloxacin, phenylbutaZone, hydrochloride, phenylpro oformine, okicenone, (commercially available as panolamine hydrochloride, polistirex, ZYPREXAR) from Eli Lilly and Company), oligonucle phenyramidol hydrochloride, phenyloin, phosphatase inhibi otides, olopatadine, olprinone, olsalazine, olsalazine Sodium, tors, physostigmine, picenadol, picibanil, picotrin diolamine, olvanil, omeprazole, onapristone, ondansetron, ontazolast, picroliv, picumeterol, pidotimod, pifamine, pilocarpine, pil oocyte maturation inhibitor, hydrochloride, ora Sicamide, pimagedine, pimetine hydrochloride, pimilprost, cin, orconazole nitrate, orgotein, orlislat, ormaplatin, orme pimobendan, pimozide, pinacidil, pinadoline, , pin toprim, ornidazole, orpanoxin, orphenadrine citrate, osater nenol, pinocebrin, hydrochloride, pioglitaZone one, otenZepad, oxacillin Sodium, oxagrelate, oxaliplatin, (commercially available as ACTOSR) from Takeda Pharma oXamarin hydrochloride, oxamisole, oxamniquine, oxan ceuticals), , pipazethate, pipecuronium bro drolone, oxantel pamoate, hydrochloride, mide, piperacetazine, piperacillin Sodium, piperamide male oxaprozin, oxarbazole, Oxatomide, oxaunomycin, oxazepam, ate, , pipobroman, piposulfan, oXcarbazepine, Oxendolone, oxethazaine, fuma palmitate, pipoxolan hydrochloride, piprozolin, piquindone rate, Oxfendazole, Oxfenicine, Oxibendazole, oxiconazole, hydrochloride, piquizil hydrochloride, piracetam, piran oxidopamine, oxidronic acid, oxifungin hydrochloride, damine hydrochloride, pirarubicin, piraZmonam Sodium, oXilorphan, oximonam, oximonam sodium, OXiperomide, piraZolac, pirbenicillin Sodium, acetate, piremper oxiracetam, oxiramide, Oxisuran, oxmetidine hydrochloride, one, pirenzepine hydrochloride, piretanide, pirfenidone, piri oXodipine, oxogestone phenpropionate, oxolinic acid, Oxpre dicillin Sodium, piridironate sodium, piriprost, piritrexim, nolol hydrochloride, oxtriphylline, oxybutynin chloride, oxy pirlimycin hydrochloride, pirlindole, pirmagrel, pirmenol chlorosene, oxycodone, hydrochloride, hydrochloride, pirnabine, piroctone, pirodavir, pirodomast, oxymetholone, oxymorphone hydrochloride, oxypertine, pirogliride tartrate, pirolate, pirolaZamide, piroxantrone oxyphenbutaZone, oxypurinol, oxytetracycline, oxytocin, hydrochloride, piroxicam, piroXimone, pirprofen, pirquino oZagrel, oZolinone, paclitaxel, palauamine, paldimycin, pali Zol, pirsidomine, prenylamine, pitavastatin (commercially navir, (commercially available as INVEGAR) available as LIVALOAR) from Eli Lilly and Company), pitu from Janssen Pharmaceuticals, Inc.), paliperidone palmitate itary, posterior, pivampicillin hydrochloride, pivopril, pizoty (commercially available as INVEGAR SUSTENNAR) from line, placetin A, platinum compounds, platinum-triamine Janssen Pharmaceuticals, Inc.), palmitoylrhizoxin, palmox complex, plicamycin, plomestane, pobilukast edamine, irate Sodium, pamaqueside, Sulfate, pamicogrel, podofilox, poisonoak extract, poldine methylsulfate, poli pamidronate disodium, pamidronic acid, panadiplon, pan glusam, polignate Sodium, polymyxin B sulfate, polythiaz amesine, panaxytriol, pancopride, pancuronium bromide, ide, ponalrestat, porfimer Sodium, porfiromycin, potassium panipenem, pannorin, panomifene, pantethine, pantoprazole, chloride, potassium iodide, potassium permanganate, povi papaverine hydrochloride, parabactin, parachlorophenol, done-iodine, , pralidoxime chloride, pramiracetam paraldehyde, paramethasone acetate, paranyline hydrochlo hydrochloride, pramoxine hydrochloride, pranolium chlo ride, parapenzolate bromide, pararosaniline pamoate, par ride, prasugrel (commercially available as EFFIENTR) from bendazole, parconazole hydrochloride, paregoric, pareptide Eli Lilly and Company), pravadoline maleate, pravastatin, Sulfate, pargyline hydrochloride, parnaparin Sodium, paro prazepam, , praZosin hydrochloride, prednazate, momycin Sulfate, paroxetine (commercially available as prednicarbate, prednimustine, prednisolone, prednisone, PAXILR) from GlaxoSmithKlein), parthenolide, partricin, prednival, pregabalin (commercially available as LYRICAR) paulomycin, paZelliptine, paZinaclone, paZoxide, paZufloxa from Pfizer, Inc.), pregnenolone Succiniate, cin, pefloxacin, pegaspargase, pegorgotein, hydro hydrochloride, pridefine hydrochloride, prifelone, prilocalne chloride, peldesine, peliomycin, pelretin, pelrinone hydro hydrochloride, priloSec, primaquine phosphate, . chloride, pemedolac, pemerid nitrate, pemetrexed, primidone, prinivil, prinomide tromethamine, prinoXodan, US 2014/0113826 A1 Apr. 24, 2014

prizidilol hydrochloride, proadifen hydrochloride, available as CRESTORR) available from AstraZeneca), probenecid, probicromil calcium, probucol, procainamide roXaitidine, roXarsone, roXindole, roXithromycin, rubiginone hydrochloride, procaine hydrochloride, procarbazine hydro B1, ruboxyl, rufloxacin, rupatidine, rutamycin, ruzadolane, chloride, hydrochloride, , proci sabeluzole, Safingol, Safironil, Saintopin, , sal nonide, proclonol, procyclidine hydrochloride, prodilidine colex, Salethamide maleate, Salicyl alcohol, salicylamide, hydrochloride, prodolic acid, profadol hydrochloride, proga salicylate meglumine, Salicylic acid, , Salnacedin, bide, progesterone, proglumide, proinsulin human, proline, Salsalate, sameridine, Sampatrilat, sancycline, Sanfetrinem, prolintane hydrochloride, hydrochloride, promet sanguinarium chloride, Saperconazole, saprisartan, saprop hazine hydrochloride, hydrochloride, propager terin, saquinavir, Sarafloxacin hydrochloride, Saralasin manium, propanidid, propantheline bromide, proparacaine acetate, SarCNU, sarcophytol A, SargramoStim, Sarmoxicil hydrochloride, propatyl nitrate, propentofylline, propen lin, Sarpicillin, Sarpogrelate, Saruplase, Saterinone, satigrel, Zolate hydrochloride, propikacin, propiomazine, propionic Satumomab pendetide, Schick test control, scopafungin, Sco acid, propionylcarnitine, propiram, propiram-paracetamol. polamine hydrobromide, Scrazaipine hydrochloride, Sdi 1 propiverine, propofol, propoxycaine hydrochloride, pro mimetics, secalciferol, secobarbital. Seelzone, seglitide poxyphene hydrochloride, hydrochloride, pro acetate, selegiline, selegiline hydrochloride, selenium Sul pulsid, propyl bis-acridone, propylhexedrine, propyliodone, fide, selenomethionine se 75, selfotel, sematilide, semdu propylthiouracil, produaZone, prorenoate potassium, ramicin, semotiadil, Semustine, sense oligonucleotides, sepa proroxan hydrochloride, proscillaridin, prostalene, prostra Zonium chloride, Seperidol hydrochloride, Seprilose, tin, protamine Sulfate, protegrin, protirelin, protoSufloxacin, seproxetine hydrochloride, seractide acetate, Sergolexole hydrochloride, proxazole, proxazole citrate, maleate, serine, sermetacin, sermorelin acetate, Sertacona proXicromil, proXorphan tartrate, prulifloxacin, pseudoephe Zole, , Sertraline, , Setoperone, Sevirumab, drine hydrochloride, desloratadine/ sulfate sevoflurane, Sezolamide, Sibopirdine, sibutramine hydrochlo (commercially available as CLARINEX-DR) from Merck), ride, signal transduction inhibitors, silandrone, Sildenafil puromycin, purpurins, pyrabrom, pyrantel, pamoate, pyrazi (commercially available as VIAGRAR) from Pfizer Inc.), sil namide, pyrazofurin, pyrazoloacridine, pyridostigmine bro ipide, silteplase, silver nitrate, Simendan, SimtraZene, simv mide, pyrilamine maleate, pyrimethamine, pyrinoline, astatin (commercially available as ZOCORR) from Merck), pyrithione sodium, pyrithione Zinc, pyrovalerone hydrochlo sincalide, sinefungin, sinitrodil, sinnabidol, sipatrigine, ride, pyroxamine maleate, pyrrocaine, pyrroliphene hydro Sirolimus, Sisomicin, Sitogluside, sizofuran, Sobuzoxane, chloride, pyrrolinitrin, pyrvinium pamoate, quadazocine sodium amylosulfate, sodium iodide I 123, sodium nitroprus meSylate, quaZepam, quaZinone, quaZodine, quaZolast, que side, Sodium oxybate, Sodium phenylacetate, sodium salicy tiapine (commercially available as SEROQUEL(R) available late, Solverol, Solypertine tartrate, Somalapor, Somantadine from AstraZenica), quiflapon, quinagolide, quinaldine blue, hydrochloride, Somatomedin B, Somatomedin C, somatrem, quinapril, quinaprilat, hydrochloride, quinbolone, Somatropin, somenopor, somidobove, Sonermin, Sorbinil, quinctolate, quindecamine acetate, quindonium bromide, Sorivudine, , Soterenol hydrochloride, sparfloxacin, quinelorane hydrochloride, quinestrol, quinfamide, sparfosate sodium, Sparfosic acid, sparsomycin, Sparteine quingestanol acetate, quingestrone, gluconate, qui Sulfate, spectinomycin hydrochloride, spicamycin D, spiper nielorane hydrochloride, quinine Sulfate, quinpirole hydro one, spiradoline mesylate, spiramycin, spirapril hydrochlo chloride, quinterenol Sulfate, quinuclium bromide, quinupris ride, spiraprilat, spirogermanium hydrochloride, Spiromus tin, quipazine maleate, rabeprazole Sodium, racephenicol, tine, Spironolactone, Spiroplatin, spiroXasone, splenopentin, racepinephrine, rafantagonists, rafoxanide, ralitoline, raloX spongistatin 1, Sprodiamide, squalamine, stallimycin hydro ifene, raltitrexed, ramatroban, ramipril, ramoplanin, ramo chloride, Stannous pyrophosphate, Stannous Sulfur colloid, setron, ranelic acid, ranimycin, ranitidine, ranolazine, rau stanozolol, statolon, staurosporine, stavudine, Steffimycin, wolfia Serpentina, recainam, recainam hydrochloride, Stenbolone acetate, Stepronin, Stilbazium iodide, stilonium reclazepam, regavirumab, regramostim, relaxin, relomycin, iodide, stipiamide, Stiripentol, Stobadine, streptomycin Sul remacemide hydrochloride, remifentanil hydrochloride, fate, Streptonicozid, streptonigrin, Streptozocin, Stromelysin remiprostol, remoxipride, repirinast, repromicin, inhibitors, strontium chloride Sr 89, succibun, succimer, suc hydrochloride, reserpine, resinferatoxin, resorcinol, retellip cinylcholine chloride, Sucralfate. Sucrosofate potassium, tine demethylated, reticulon, reviparin Sodium, revizinone, Sudoxicam, Sufentanil, Sufotidine, Sulazepam, Sulbactam piv rhenium re 186 etidronate, rhizoxin, ribaminol, ribavirin, oxil, Sulconazole nitrate, Sulfabenz, Sulfabenzamide, Sulfac riboprine, ribozymes, ricasetron, ridogrel, rifabutin, rifamet etamide, Sulfacytine, Sulfadiazine, Sulfadoxine, Sulfalene, ane, rifamexil, rifamide, rifampin, rifapentine, rifaximin, reti Sulfamerazine, Sulfameter, Sulfamethazine, Sulfamethizole, namide, rilopiroX, riluzole, rimantadine, rimcazole hydro Sulfamethoxazole, Sulfamonomethoxine, Sulfamoxole, Sulfa chloride, rimexolone, hydrobromide, rimoprogin, nilate Zinc, Sulfanitran, Sulfasalazine, Sulfasomizole, Sul riodipine, rioprostil, ripazepam, ripisartan, risedronate fazamet, hydrochloride, Sulfinosine, Sulfinpyra Sodium, risedronic acid, risocaine, risotilide hydrochloride, Zone, Sulfisoxazole, Sulfomyxin, Sulfonterol hydrochloride, rispenzepine, risperdal, , , ritipenem, Sulfoxamine, Sulinldac, Sulmarin, Sulnidazole, Suloctidil, , ritolukast, ritonavir, rizatriptan benzoate, rocastine Sulofenur, Sulopenem, Suloxifen oxalate, Sulpiride, Sulpros hydrochloride, rocuronium bromide, rodocaine, roflurane, tone, Sultamicillin, Sulthiame, Sultopride, Sulukast, Sumaro rogletimide, rohitukine, rokitamycin, roletamicide, rolgami tene, Sumatriptan, Suncillin Sodium, Suproclone, Suprofen, dine, rolicyprine, rolipram, rollitetracycline, rolodine, romaz Suradista, Suramin, Surfomer, Suricamide maleate, SuritoZole, arit, romurtide, ronidazole, ropinirole (commercially avail Suronacrine maleate, Suxemerid Sulfate, Swainsonine, able as REQUIPR) from GlaxoSmithKline), ropitoin Symakalim, Symclosene, Symetine hydrochloride, synthetic hydrochloride, ropivacaine, ropizine, roquinimex, rosarami glycosaminoglycans, tadalafil (commercially available as cin, roSoxacin, rotoxamine, rosuvastatin (commercially CIALIS(R) and ACIRCAR) from from Eli Lilly and Company), US 2014/0113826 A1 Apr. 24, 2014

taciamine hydrochloride, tacrine hydrochloride, tacrolimus, amic acid, tranilast, transcamide, translation inhibitors, tras talampicillin hydrochloride, taleranol, talisomycin, tallimus tuzumab (commercially available as HERCEPTINR) from tine, talmetacin, talniflumate, talopram hydrochloride, talos Genentech), traXanox, hydrochloride, traZodone alate, tametraline hydrochloride, tamoxifen (commercially hcl, trebenzomine hydrochloride, trefentanil hydrochloride, available as NOLVADEXOR) from AstraZeneca), treloxinate, trepipam maleate, trestolone acetate, tretinoin, fumarate, hydrochloride, tandamine hydrochlo triacetin, triacetyluridine, triafungin, triamcinolone, triampy ride, , tapgen, taprostene, tasosartan, tauromus Zine Sulfate, triamterene, triazolam, tribenoside, tricaprilin, tine, taxane, taxoid, tazadolene Succinate, taZanolast, tazaro tricetamide, trichlormethiazide, trichohyalin, triciribine, tene, tazifylline hydrochloride, taZobactam, taZofelone, tricitrates, triclofenol piperazine, triclofos sodium, triclonide, hydrochloride, tebufelone, tebuquine, technetium Tc trientine, trifenagrel, triflavin, triflocin, triflubazam, triflumi 99 m bicisate, teclozan, tecogalan Sodium, teecleukin, teflu date, hydrochloride, trifluperidol, triflupro rane, tegafur, tegretol, teicoplanin, telenzepine, tellurapyry mazine, hydrochloride, trifluridine, trihex lium, telmesteine, telmisartan, telomerase inhibitors, teloX yphenidyl hydrochloride, triloStane, antrone hydrochloride, teludipine hydrochloride, hydrochloride, trimegestone, trimeprazine tartrate, tri temafloxacin hydrochloride, tematropium methyl Sulfate, methadione, trimethaphan camsylate, trimethobenzamide temazepam, temelastine, temocapril, temocillin, temoporfin, hydrochloride, trimethoprim, trimetozine, trimetrexate, temozolomide, tenofovir, tenidap, teniposide, tenosal, , trimoprostil, trimoxamine hydrochloride, tri tenoxicam, tepirindole, tepoxalin, teprotide, , ter olein 1 125, triolein 1131, trioxifene mesylate, tripamide, binafine, sulfate (commercially available as BRI tripelennamine hydrochloride, triprolidine hydrochloride, CANYL(R) from AstraZeneca), terconazole, terfenadine, ter triptorelin, trisulfapyrimidines, troclosene potassium, trogli flavoxate, , teriparatide acetate, terlakiren, taZone, trolamine, troleandomycin, trombodipine, trometa terlipressin, terodiline, teroxalene hydrochloride, teroxirone, mol, tropanserin hydrochloride, tropicamide, tropine ester, , tesicam, tesimide, testolactone, testosterone, tetra tropisetron, trospectomycin, trovafloxacin, troVirdine, tryp caine, tetrachlorodecaoxide, tetracycline, tetrahydrozoline tophan, tuberculin, tubocurarine chloride, tubulozole hydro hydrochloride, tetramisole hydrochloride, tetrazolast meglu chloride, tucarcsol, , turosteride, tybamate, tylo mine, tetraZomine, tetrofosmin, tetroquinone, tetroxoprim, genin, tyropanoate Sodium, , tyrothricin, tyrphostins, tetrydamine, thaliblastine, thalidomide, theofibrate, theo ubenimex, uldazepam, undecylenic acid, uracil mustard, ura phylline, thiabendazole, thiamiprine, thiamphenicol, thiamy pidil, urea, uredepa, uridine triphosphate, urofollitropin, lal, thiazesim hydrochloride, thiazinamium chloride, thiazo urokinase, ursodiol, Valaciclovir, Valine, valnoctamide, val lidinedione, thiethylperazine, thimerfonate Sodium, proate Sodium, Valproic acid, Valsartan (commercially avail thimerosal, thiocoraline, thiofedrine, thioguanine, thiomar able as DIOVANR) from Novartis Pharmaceuticals), vamica inol, thiopental sodium, thioperamide, , thiotepa, mide, Vanadeine, Vancomycin, Vaminolol, Vapiprost thiothixene, thiphenamil hydrochloride, thiphencillin potas hydrochloride, vapreotide, Vardenafil (commercially avail sium, thiram, thozalinone, threonine, thrombin, thrombopoi able as LEVITRAR) from GlaxoSmithKline), variolin B, etin, thrombopoietin mimetic, thymalfasin, thymopoietin vasopressin, Vecuronium bromide, Velaresol, Velnacrine receptor agonist, thymotrinan, thyromedan hydrochloride, maleate, Venlafaxine, Veradoline hydrochloride, Veramine, thyroxine 1 125, thyroxine 1131, tiacrilast, tiacrilast sodium, Verapamil hydrochloride, verdins, verilopam hydrochloride, tiagabine, , tianeptine, tiapafant, tiapamil hydro Verlukast, Verofylline, Veroxan, Verteporfin, Vesnarinone, chloride, tiaramide hydrochloride, tiazofurin, tibenelast vexibinol, Vidarabine, vigabatrin, viloxazine hydrochloride, Sodium, tibolone, tibric acid, ticabesone propionate, ticarbo vinblastine Sulfate, vinburnine citrate, Vincofos, Vinconate, dine, ticarcillin cresyl Sodium, ticlatone, ticlopidine, tic Vincristine Sulfate, vindesine, vindesine Sulfate, vinepidine rynafen, , tifurac sodium, tigemonam dicholine, Sulfate, Vinglycinate Sulfate, Vinleurosine Sulfate, vinorel tigestol, tiletamine hydrochloride, tilidine hydrochloride, til bine, Vinpocetine, Vintoperol, Vinxaltine, Vinzolidine Sulfate, isolol, tilnoprofen arbamel, tillorone hydrochloride, tiludr Viprostol, Virginiamycin, viridofulvin, ViroXime, vitaxin, onate disodium, tiludronic acid, timefurone, timobesone Volazocine, Voriconazole, Vorozole, VOXergolide, warfarin acetate, , tin ethyl etiopurpurin, tinabinol, tinidazole, Sodium, , Xanomeline, XanoXate Sodium, Xanthinol tinzaparin sodium, tioconazole, , tiodonium chlo niacinate, Xemilofiban, Xenalipin, Xenbucin, Xilobam, Ximo ride, tioperidone hydrochloride, tiopinac, hydro profen, Xipamide, Xorphanol mesylate, Xylamidine tosylate, chloride, tiotidine, tiotropium bromide, tioxidazole, tipen hydrochloride, hydrochloride, tosin hydrochloride, tipredane, hydrochloride, Xylose, yangambin, Zabicipril, Zacopride, Zafirlukast, Zalcit tiprinast meglumine, tipropidil hydrochloride, tiqueside, abine, Zaleplon, Zalospirone, Zaltidine hydrochloride, Zalto tiquinamide hydrochloride, tirandalydigin, tirapazamine, tir profen, Zanamivir, Zankiren, Zanoterone, Zantac, Zarirlukast, ilazad, tirofiban, tiropramide, titanocene dichloride, tixanox, Zatebradine, Zatosetron, Zatosetron maleate, Zenarestat, Zena tiXocortol pivalate, hydrochloride, tobramycin, Zocine mesylate, Zeniplatin, Zeranol, Zidometacin, Zidovu tocainide, tocamphyl, tofenacin hydrochloride, . dine, Zifrosilone, Zilantel, Zilascorb, Zileuton, Zimeldine tolazamide, hydrochloride, tolbutamide, tolca hydrochloride, Zinc undecylenate, Zindotrine, Zinoconazole pone, tolciclate, tolfamide, tolgabide, lamotrigine, tolimi hydrochloride, Zinostatin, hydrochloride, Zin done, tolindate, tolmetin, tolnaftate, tolpovidone 1 131, ViroXime, , Zobolt, Zofenopril calcium, Zofenop tolpyrramide, tolrestat, tomelukast, tomoxetine hydrochlo rilat, Zolamine hydrochloride, Zolazepam hydrochloride, ride, tonazocine mesylate, topiramate, topotecan, topotecan Zoledronie acid, Zollertine hydrochloride, Zolmitriptan, Zolpi hydrochloride, top sentin, topterone, toguizine, torasemide, dem, Zomepirac sodium, Zometapine, ZonicleZole hydrochlo toremifene, torsemide, tosifen, to Sufloxacin, totipotent stem ride, Zonisamide, Zopiclone, Zopolrestat, Zorbamycin, Zoru cell factor, tracazolate, trafermin, tralonide, tramadol hydro bicin hydrochloride, , Zucapsaicin, JTT-501 (PNU chloride, tramazoline hydrochloride, trandolapril, tranex 182716) (reglitazar), AR-HO39122, MCC-555 US 2014/0113826 A1 Apr. 24, 2014

(netoglitazone), AR-HO49020 (tesaglitazar), CS-011 (CI lamine antifungals (e.g., terbinafine (commercially available 1037), GW-409544x, KRP-297, RG-12525, BM-15.2054, as LAMISILR from Novartis Consumer Health, Inc.), nafti CLX-0940, CLX-0921, DRF-2189, GW-1929, GW-9820, fine (commercially available as NAFTINR) available from LR-90, LY-510929, NIP-221, NIP-223, JTP-20993, LY Merz Pharmaceuticals), and butenafine (commercially avail 29311 Na, FK 614, BMS 298.585, R 483, TAK 559, DRF able as LOTRAMINULTRAR) from Merck), echinocandin 2725 (ragaglitazar), L-686398, L-168049, L-805645, antifungals (e.g., anidulafungin, caspofungin, and micafun L-054852, demethyl asteriquinone B1 (L-783281), gin), polygodial, benzoic acid, ciclopiroX, tolnaftate (e.g., L-363586, KRP-297, P32/98, CRE-16336, EML-1625, phar commercially available as TINACTINR) from MDS Con maceutically acceptable salts thereof (e.g., Zn, Fe,Mg, K, Na, Sumer Care, Inc.), undecylenic acid, flucytosine, 5-fluorocy F, CI, Br, I, acetate, diacetate, nitrate, nitrite, sulfate, sulfite, tosine, griseofulvin, haloprogin, and any combination phosphate, and phosphite salts), pharmaceutically acceptable thereof. forms thereof with acid associates (e.g. HCl), and any com bination thereof. 0.095 Examples of active biologicals may include, but are not limited to, hormones (synthetic or natural and patient 0093 Examples of antibiotics may include, but are not derived or otherwise), DNAs (synthetic or natural and patient limited to, to B-lactam antibiotics (e.g., benzathine penicillin, derived or otherwise), RNAs (synthetic or natural and patient benzylpenicillin (penicillin G), phenoxymethylpenicillin derived or otherwise), siRNAs (synthetic or natural and (penicillin V), procaine penicillin, methicillin, oxacillin, patient derived or otherwise), proteins and peptides (e.g., nafcillin, cloxacillin, dicloxacillin, flucloxacillin, temocillin, albumin, atrial natriuretic factor, renin, Superoxide dismu amoxicillin, amplicillin, co-amoxiclav (amoxicillin+clavu tase, C.1-antitrypsin, lung Surfactant proteins, bacitracin, lanic acid), azlocillin, carbenicillin, ticarcillin, mezlocillin, bestatin, cydosporine, delta sleep-inducing peptide (DSIP), piperacillin, cephalosporin, cephalexin, cephalothin, cefazo endorphins, glucagon, gramicidin, melanocyte inhibiting fac lin, cefaclor, cefuroxime, cefamandole, cefotetan, cefoxitin, tors, neurotensin, oxytocin, Somostatin, terprotide, serum ceftriaxone, cefotaxime, cefpodoxime, cefixime, ceftazi thymide factor, thymosin, DDAVP, dermorphin, Met-en dime, cefepime, cefpirome, carbapenem, imipenem (with cil kephalin, peptidoglycan, Satietin, thymopentin, fibrin degra astatin), meropenem, ertapenem, faropenem, doripenem, dation product, des-enkephalin-C-endorphin, gonadotropin aztreonam (commercially available as AZACTAM(R) from releasing hormone, leuprolide, C-MSH, and metkephamid), Bristol-Myers Squibb), tigemonam, nocardicin A, tabtoxi enzymes, nucleotides, oligionucleotides, antibodies, mono nine-B-lactam, clavulanic acid, taZobactam, and Sulbactam); clonal antibodies, growth factors (e.g., epidermal growth fac aminoglycoside antibiotics (e.g., aminoglycoside, amikacin, tor (EGF), fibroblast growth factors, basic fibroblast growth apramycin, arbekacin, astromicin, bekanamycin, capreomy factor (bFGF), nerve growth factor (NGF), bone derived cin, dibekacin, dihydrostreptomycin, elsamitrucin, G418, growth factor (BDGF), transforming growth factors, trans gentamicin, hygromycin B, isepamicin, kanamycin, kasuga forming growth factor-131 (TGF-131), and human growth mycin, micronomicin, neomycin, netilmicin, paromomycin gormone (hGH)), Viral Surface antigens (e.g., adenoviruses, Sulfate, ribostamycin, Sisomicin, Streptoduocin, Streptomy epstein-barr virus, hepatitis A virus, hepatitis B virus, herpes cin, tobramycin, Verdamicin; Sulfonamides such as Sul viruses, HIV-1, HIV-2, HTLV-III, influenza viruses, Japanese famethoxazole, Sulfisomidine (also known as Sulfaisodimi encephalitis virus, measles virus, papilloma viruses, dine), sulfacetamide, sulfadoxine, dichlorphenamide (DCP), paramyxoviruses, polio virus, rabies virus, rubella virus, vac and dorzolamide); quinolone antibiotics (e.g., cinobac, cinia (Smallpox) viruses, and yellow fever virus), bacterial flumequine, nalidixic acid, OXolinic acid, piromidic acid, Surface antigens (e.g., bordetella pertussis, helicobacter pipemidic acid, roSoxacin, ciprofloxacin, enoxacin, fleroxa pylorn, clostridium tetani, corynebacterium diphtheria, cin, lomefloxacin, nadifloxacin, norfloxacin, ofloxacin, escherichia coli, haemophilus influenza, klebsiella species, pefloxacin, rufloxacin, balofloxacin, grepafloxacin, levof legionella pneumophila, mycobacterium bovis, mycobacte loxacin, paZufloxacin, sparfloxacin, temafloxacin, to Sufloxa rium leprae, mycrobacterium tuberculosis, neisseria gonor cin, clinafloxacin, gatifloxacin, gemifloxacin, moxifloxacin, rhoeae, neisseria meningitidis, proteus species, pseudomo sitafloxacin, trovafloxacin, prulifloxacin, garenoxacin, and nas aeruginosa, Salmonella species, Shigella species, delafloxacin); oxazolidone antibiotics (e.g., lineZolid, tor staphylococcus aureus, Streptococcus pyogenes, vibrio chol eZolid, eperezolid, posiZolid, and radeZolid), and any combi era, and versinia pestis), parasite Surface antigens (e.g., plas nation thereof. modium vivax—malaria, plasmodium falciparum—malaria, 0094. Examples of antifungals suitable may include, but plasmodium ovale—malaria, plasmodium malariae—ma are not limited to, polyene antifungals (e.g., natamycin, rimo laria, leishmania tropica—leishmaniasis, leishmania dono cidin, filipin, nystatin, amphotericin B, candicin, and hamy vani, leishmaniasis, leishmania branziliensis—leishmania cin, imidazole antifungals such as miconazole (commercially sis, trypanosoma rhodescense—sleeping sickness, available as MICATINR) from WellSpring Pharmaceutical trypanosoma gambiense—sleeping sickness, trypanosoma Corporation), ketoconazole (commercially available as cruzi—Chagas disease, schistosoma mansoni—Schistoso NIZORAL(R) from McNeil consumer Healthcare), clotrima miasis, schistosomona haematobium—schistomiasis, Schis zole(commercially available as LOTRAMINR) and LOTRA tosoma japonicum—shichtomiasis, trichinella spiralis—tri MIN AF(R) available from Merck and CANESTENR) avail chinosis, stronglyloides duodenale hookworm, able from Bayer), econazole, omoconazole, bifonazole, ancyclostoma duodenale hookworm, necator america butoconazole, fenticonazole, isoconazole, oxiconazole, nus—hookworm, wucheria bancrofti—filariasis, brugia sertaconazole (commercially available as ERTACZOR from malaya—filariasis, loa loa—filariasis, dipetalonema per OrthoDematologics), Sulconazole, and tioconazole; triazole staris—filariasis, dracuncula medimensis—filariasis, and antifungals such as fluconazole, itraconazole, isaVuconazole, Onchocerca volvulus—filariasis), immunogobulins (e.g., raVuconazole, posaconazole, Voriconazole, terconazole, and IgG, IgA, IgM, antirabies immunoglobulin, and antivaccinia albaconazole), thiazole antifungals (e.g., abafungin), ally immunoglobulin), and any combination thereof. US 2014/0113826 A1 Apr. 24, 2014

0096. Examples of antitoxins may include, but are not butyrate, pentylpentanoate, octyl acetate, myrcene, geraniol, limited to, botulinum antitoxin, diphtheria antitoxin, gas gan nerol, citral, citronellal, citronellol, linalool, nerolidol, grene antitoxin, tetanus antitoxin, and any combination limonene, camphor, terpineol, alpha-ionone, thujone, benzal thereof. dehyde, eugenol, cinnamaldehyde, ethyl maltol, Vanilla, ani 0097 Examples of antigents may include, but are not lim sole, anethole, estragole, thymol, furaneol, methanol, rose ited to, foot and mouth disease, hormones and growth factors mary, lavender, citrus, freesia, apricot blossoms, greens, (e.g., follicle stimulating hormone, prolactin, angiogenin, peach, jasmine, rosewood, pine, thyme, oakmoss, musk, epidermal growth factor, calcitonin, erythropoietin, thyrotro Vetiver, myrrh, blackcurrant, bergamot, grapefruit, acacia, pic releasing hormone, insulin, growth hormones, insulin passiflora, Sandalwood, tonka bean, mandarin, neroli, violet like growth factors 1 and 2, skeletal growth factor, human leaves, gardenia, red fruits, ylang-ylang, acacia farnesiana, chorionic gonadotropin, luteinizing hormone, nerve growth mimosa, tonka bean, woods, ambergris, daffodil, hyacinth, factor, adrenocorticotropic hormone (ACTH), luteinizing narcissus, black currant bud, iris, raspberry, lily of the valley, hormone releasing hormone (LHRH), parathyroid hormone sandalwood, Vetiver, cedarwood, neroli, bergamot, Straw (PTH), thyrotropin releasing hormone (TRH), vasopressin, berry, carnation, oregano, honey, civet, heliotrope, caramel, cholecystokinin, and corticotropin releasing hormone), coumarin, patchouli, dewberry, helonial, bergamot, hyacinth, cytokines (e.g., interferons, interleukins, colony stimulating coriander, pimento berry, labdanum, cassie, bergamot, alde factors, and tumor necrosis factors: fibrinolytic enzymes, hydes, orchid, amber, benzoin, orris, tuberose, palmarosa, Such as urokinase, kidney plasminogen activator), clotting cinnamon, nutmeg, moss, Styrax, pineapple, bergamot, fox factors (e.g., Protein C, Factor VIII, Factor IX, Factor VII and glove, tulip, wisteria, clematis, ambergris, gums, resins, civet, Antithrombin III), and any combination thereof. peach, plum, castoreum, civet, myrrh, geranium, rose violet, 0098. Examples of nutritional supplements may include, jonquil, spicy carnation, galbanum, hyacinth, petitgrain, iris, but are not limited to, Vitamins, minerals, herbs, botanicals, hyacinth, honeysuckle, pepper, raspberry, benzoin, mango, amino acids, steroids, and the like. coconut, hesperides, castoreum, osmanthus, mousse de 0099 Examples of imaging agents may include, but are chene, nectarine, mint, anise, cinnamon, orris, apricot, not limited to, iron oxide, gadolinium ions, iodine, perfluo plumeria, marigold, rose otto, narcissus, tolu balsam, frank rocarbons, radioisotopes, and the like. incense, amber, orange blossom, bourbon Vetiver, opopanax, 0100 Examples of fluid stabilizers may include, but are white musk, papaya, Sugar candy, jackfruit, honeydew, lotus not limited to, at least one component of citrate phosphate blossom, muguet, mulberry, absinthe, ginger, juniper berries, with dextrose buffer (e.g., stabilizing blood), blood clotting spicebush, peony, violet, lemon, lime, hibiscus, white rum, factors, emulsion stabilizers, antifoamers, agar, pectin, and basil, lavender, balsamics, fo-ti-tieng, osmanthus, karo the like, and any combination thereof. karunde, white orchid, calla lilies, white rose, rhubrum lily, 0101 Examples of food agents may include, but are not tagetes, ambergris, ivy, grass, seringa, Spearmint, clary sage, limited to, caffeine, flavors, aromas, vitamins, minerals, cottonwood, grapes, brimbelle, lotus, cyclamen, orchid, gly herbs, minerals, antioxidants, calcium propionate, sodium cine, tiare flower, ginger lily, green osmanthus, passion nitrate, sodium nitrite, Sulfites, Sulfur dioxide, sodium flower, blue rose, bay rum, cassie, Africantagetes, Anatolian bisulfite, potassium hydrogen sulfite, disodium EDTA, salt, rose, Auvergne narcissus, British broom, British broom rosemary extract, Sugar, low-calorie Sweeteners, no-calorie chocolate, Bulgarian rose, Chinese patchouli, Chinese garde Sweeteners, vinegar, alcohol, hops, diatomaceous earth, and nia, Calabrian mandarin, Comoros Island tuberose, Cey the like, and any combination thereof. lonese cardamom, Caribbean passion fruit, Damascena rose, 0102) Examples of nutraceuticals may include, but are not Georgia peach, white Madonna lily, Egyptian jasmine, Egyp limited to, dietary Supplements, botanicals, functional foods tian marigold, Ethiopian civet, Farnesian cassie, Florentine and extracts thereof, medicinal foods and extracts thereof, iris, French jasmine, French jonquil, French hyacinth, Guinea Vitamins, minerals, co-enzyme Q, carnitine, multi-mineral oranges, Guyana wacapua, Grasse petitgrain, Grasse rose, formulas, ginseng, gingko biloba, saw palmetto, other plant Grasse tuberose, Haitian Vetiver, Hawaiian pineapple, Israeli based Supplements, probiotics, omega-3, canola and other basil, Indian sandalwood, Indian Ocean Vanilla, Italian ber oils, plant stanols, natural Sweeteners, mushroom extracts, gamot, Italian iris, Jamaican pepper, May rose, Madagascar chocolate, chocolate extracts, grape extracts, berry extracts, ylang-ylang, Madagascar Vanilla, Moroccan jasmine, Moroc Super food extracts, quillaja molina extracts, plant extracts, can rose, Moroccan oakmoss, Moroccan orange blossom, yucca Schidigera extract, bran, alanine, beta-carotene, caro Mysore sandalwood, Oriental rose, Russian leather, Russian tenoids, arginin, vitamin A, asparagine, Vitamin B-complex, coriander, Sicilian mandarin, South African marigold, South aspartate, Vitamin C, leucine, isoleucine, Valine, Vitamin D, American tonka bean, Singapore patchouli, Spanish orange citrulline, Vitamin E, cysteine, Vitamin K, glutamine, miner blossom, Sicilian lime, Reunion Island Vetiver, Turkish rose, als, micro-nutrients, glutamic acid, calcium, glycine, chro Thai benzoin, Tunisian orange blossom, Yugoslavian oak mium, histidine, copper, lysine, iodine, methionine, iron, moss, Virginian cedarwood, Utah yarrow, West Indian rose ornithine, magnesium, phenylalanine, potassium, proline, wood, and the like, and any combination thereof. Selenium, serine, Zinc, taurine, threonine, alpha lipoic acid, 0104 Examples of flavorants may include, but are not tryptophan, green tea extracts, tyrosine, essential fatty acids limited to, tobacco, menthol, cloves, cherry, chocolate, (EFA), whey protein, flax seed oil, and any combination orange, mint, mango, Vanilla, cinnamon, and the like. Such thereof. flavorants may, in some embodiments, be provided by men 0103 Examples of olfactory agents may include, but are thol, anethole (licorice), anisole, limonene (citrus), eugenol not limited to, spices, spice extracts, herb extracts, essential (clove), a flavorant associated with an olfactory agent oils, Smelling salts, Volatile organic compounds, Volatile described herein, and the like, and any combination thereof. Small molecules, methyl formate, methyl acetate, methyl 0105 Examples of plant agents may include, but are not butyrate, ethyl acetate, ethylbutyrate, isoamyl acetate, pentyl limited to, herbicides, fungicides, insecticides, bactericides, US 2014/0113826 A1 Apr. 24, 2014 nitrogen sources, phosphorous sources, potassium sources, ester and a solvent; diluting the polysaccharide ester product, calcium sources, magnesium sources, Sulfur sources, boron thereby yielding a polysaccharide ester dope; and forming a Sources, chlorine sources, copper sources, iron Sources, man plurality of polysaccharide ester microspheres from the ganese sources, molybdenum sources, Zinc sources, saltpeter, polysaccharide ester dope. Optionally, at least one of the growth promoters, hormones, and the like, and any combina following elements may be included in the method: Element tion thereof. 1: the method further including filtering the polysaccharide 0106 Examples of chemical-reaction agents may include, ester product before diluting; Element 2: wherein the but are not limited to, positive catalysts, inhibitors, and the polysaccharide ester comprises at least one ester derivative of like, and any combination thereof. at least one selected from the group consisting of starch, 0107 As used herein, the term “insect repellent” refers to cellulose, hemicellulose, algenates, chitosan, and any combi both insect repellents and insecticides. One skilled in the art nation thereof. Element 3: Element 2 wherein the ester with the benefit of this disclosure should understand that derivative comprises at least one organic ester Substituent because controlled release vehicles described herein, in some selected from the group consisting of an C-Co aliphatic embodiments, are designed to be administered to a patient, ester, a functional C-C aliphatic ester, an aromatic ester, a insect repellents should be chosen that are compatible with Substituted aromatic ester, any derivative thereof, and any Such a desired administration technique. Examples of insect combination thereof. Element 4: Element 2 wherein the ester repellents may include, but are not limited to, natural repel derivative comprises at least one inorganic ester Substituent lents (e.g., essential oils, citronella, Sodium laurel Sulfate, selected from the group consisting of hypochlorite, chlorite, cedar, neem, clove, thyme, lavender, eucalyptus, peppermint, chlorate, perchlorate, Sulfite, Sulfate, a Sulfonate, fluorosul lemongrass, garlic, capsaicin, Sabadillia, rotenone, nicotine, fate, nitrite, nitrate, phosphite, phosphate, phosphonates, and pyrethrum), synthetic repellents (e.g., N,N-dimethyl borate, any derivative thereof, and any combination thereof; meta-toluamide (DEET), dichlorodiphenyltrichloroethane Element 5: wherein the polysaccharide ester comprises at (DDT), organophosphate-based insecticides, pyrethroids, least one ester derivative of starch and at least one ester picaridin, boric acid, cyfluthrin, deltamethrin, fenthion, pro derivative of cellulose; Element 6: Element 5 wherein the poXur, Sevin, dinotefuran, acephate, chlorophyrifos, diazi polysaccharide ester dope has a Solids content of about 4% to non, horticultural oil, malathion, and methoxyclor), insect about 50% by weight of the polysaccharide ester dope; and controlling pheromones, and the like, and any combination Element 7: whereinforming the plurality of polysaccharide thereof. Examples of insecticides may include, but are not ester microspheres involves spraying the polysaccharide ester limited to, acid copper chromate (ACC), acetamiprid, dope into a coagulation bath comprising a non-solvent of the bifenazate, chlorantraniliprole, chlorfenapyr, clothianidin, polysaccharide ester. Exemplary combinations of embodi dinotefuran, ethiprole, flubendiamide, flufenoxuron, imipro ments may include, but are not limited to, Element 1 in thrin, indoxacarb, metrafenone, nicarbazin, n-methylneode combination with Element 5; Element 3 in combination with canamide, phosphine, pirimicarb, pyridalyl, spinetoram, Spi Element 5; Element 3 in combination with Element 4: Ele nosad, Spirodiclofen, Spirotetramat, tebufenpyrad, ment 4 in combination with Element 5; Elements 3 and 4 in thiacloprid, pyrethrin, allethrin, prallethrin, furamethrin, phe combination with Element 5; Element 5 in combination with nothrin, permethrin, imidacloprid, pyriproxyfen Silafluofen, Element 6: Element 1 in combination with Element 6: Ele hinokitiol, isopropylmethyl phenol, 5-chloro-2-trifluo ment 3 in combination with Element 6: Element 4 in combi romethanesulfonamide methylbenzoate, tauflu valinate, flu nation with Element 6: Elements 3 and 4 in combination with methrin, trans-cyfluthrin, kadethrin, bioresmethrin, tet Element 6: Element 1 in combination with Elements 5 and 6: ramethrin, empenthrin, cyphenothrin, bioallethrin, an Element 3 in combination with Elements 5 and 6: Element 4 oxadiazine derivative, a chloronicotinyl, a nitroguanidine, a in combination with Elements 5 and 6: Elements 3 and 4 in pyrrol, a pyrazone, a diacylhydrazine, a triazole, a biological/ combination with Elements 5 and 6; and Element 7 in com fermentation product, a phenyl pyrazole, an organophos bination with any of the foregoing. phate, a carbamate, a pyrethrin, d-trans allethrin, esbiol. 0109 Exemplary embodiment B disclosed herein esbiothrin, pynamin forte, n-octyl bicycloheptenedicarbox includes: a method that includes forming a polysaccharide imide, and the like, and any combination thereof. Further, an ester product from a polysaccharide synthesis, wherein the insect repellent may be utilized, in Some embodiments, in polysaccharide ester product comprises a starch ester and a conjunction with an insect repellent synergist, a chemical or Solvent; producing a polysaccharide ester dope from the biological compound that interferes with an insects ability to polysaccharide ester product, wherein the polysaccharide mitigate the effects of an insect repellent. Examples of insect ester dope has a solids content of about 16% to about 50% by repellent synergists may include, but are not limited to, pip weight of the polysaccharide ester dope; and forming a plu eronylbutoxide, dietholate, sesamex, Sulfoxide, butcarpolate, rality of polysaccharide ester microspheres from the polysac sesamolin, jiajizengxiaolin, octachlorodipropylether, pipero charide ester dope. Optionally, at least one of the following nyl cyclonene, piprotal, propylisome, and any combination elements may be included in the method: Element 8: wherein thereof. In some embodiments, an insect repellent, and pref the polysaccharide esterproduct further comprises a cellulose erably an insect repellant that comprises an insecticide, may ester; Element 9: the method further comprising adding a be used in conjunction with compounds that attracts insects to cellulose ester to the polysaccharide ester dope: Element 10: a microsphere or article comprising microspheres described wherein the polysaccharide ester further comprises at least herein, including, but not limited to, any Suitable aroma one ester derivative of at least one selected from the group described herein. consisting of hemicellulose, algenates, chitosan, and any 0108 Exemplary embodiment A disclosed herein combination thereof. Element 11: wherein the ester deriva includes: a method that includes forming a polysaccharide tive comprises at least one organic ester Substituent selected ester product from a polysaccharide synthesis, wherein the from the group consisting of an C-Co aliphatic ester, a polysaccharide ester product comprises a polysaccharide functional C-Coaliphatic ester, an aromatic ester, a Substi US 2014/0113826 A1 Apr. 24, 2014 20 tuted aromatic ester, any derivative thereof, and any combi organic ester Substituent selected from the group consisting of nation thereof. Element 12: wherein the ester derivative com an C-C aliphatic ester, a functional C-C aliphatic ester, prises at least one inorganic ester Substituent selected from an aromatic ester, a Substituted aromatic ester, any derivative the group consisting of hypochlorite, chlorite, chlorate, per thereof, and any combination thereof; Element 17: wherein chlorate, sulfite, sulfate, a sulfonate, fluorosulfate, nitrite, the starch ester comprises at least one inorganic ester Sub nitrate, phosphite, phosphate, phosphonates, borate, any stituent selected from the group consisting of hypochlorite, derivative thereof, and any combination thereof; Element 13: chlorite, chlorate, perchlorate, Sulfite, Sulfate, a Sulfonate, wherein producing a polysaccharide ester dope involves fluorosulfate, nitrite, nitrate, phosphite, phosphate, phospho diluting the polysaccharide ester product and optionally fil nates, borate, any derivative thereof, and any combination tering the polysaccharide ester product before and/or after thereof; Element 18: wherein the microsphere further com diluting; Element 14: wherein producing a polysaccharide prises a cellulose ester; Element 19: Element 18 wherein the ester dope involves finishing the polysaccharide esterproduct cellulose ester comprises at least one organic ester Substituent and Suspending the finished polysaccharide esterproduct in a selected from the group consisting of an C-C aliphatic solvent; and Element 15: wherein forming the plurality of ester, a functional C-Coaliphatic ester, an aromatic ester, a polysaccharide ester microspheres involves spraying the Substituted aromatic ester, any derivative thereof, and any polysaccharide ester dope into a coagulation bath comprising combination thereof. Element 20: Element 18 wherein the a non-solvent of the polysaccharide ester. Exemplary combi cellulose ester comprises at least one inorganic ester Substitu nations of embodiments may include, but are not limited to, ent selected from the group consisting of hypochlorite, chlo one of Elements 8-10 in combination with Element 11; one of rite, chlorate, perchlorate, Sulfite, Sulfate, a Sulfonate, fluoro Elements 8-10 in combination with Element 12: Element 11 Sulfate, nitrite, nitrate, phosphite, phosphate, phosphonates, in combination with Element 12: Element 15 in combination borate, any derivative thereof, and any combination thereof; with any of the foregoing; and one of Elements 13 and 14 in Element 21: wherein the microsphere further comprises at combination with any of the foregoing. least one ester derivative of at least one selected from the 0110 Exemplary embodiment C disclosed herein group consisting of hemicellulose, algenates, chitosan, and includes: a method that includes providing a finished polysac any combination thereof; and Element 22: wherein the micro charide ester product that comprises a starchester, producing sphere has a surface area of about 1 m/g to about 50 m/gas a polysaccharide ester dope that comprises the finished measured by BET with nitrogen gas. Exemplary combina polysaccharide ester product and a solvent, wherein the tions of embodiments may include, but are not limited to, polysaccharide ester dope has a solids content of about 16% Element 16 in combination with Element 17; at least one of to about 50% by weight of the polysaccharide ester dope; and Elements 16 and 17 in combination with Element 18 (option forming a plurality of polysaccharide ester microspheres ally in combination with at least one of Elements 19 and 20): from the polysaccharide ester dope. Optionally, at least one of Element 18 in combination with at least one of Elements 19 the following elements may be included in the method: Ele and 20; Element 21 in combination with any of the foregoing: ment 8: wherein the polysaccharide ester product further and Element 22 in combination with any of the foregoing. comprises a cellulose ester; Element 9: the method further O112 Additional embodiments may include: comprising adding a cellulose ester to the polysaccharide 0113 E: a cosmetic comprising the polysaccharide ester ester dope; Element 10: wherein the polysaccharide ester microsphere according to Embodiment D optionally includ further comprises at least one ester derivative of at least one ing the corresponding Elements (or produced by a method of selected from the group consisting of hemicellulose, Embodiments A-C optionally including the corresponding algenates, chitosan, and any combination thereof. Element Elements) that further comprises at least one of an aroma, a 11: wherein the ester derivative comprises at least one organic flavorant, and a colorant, wherein the cosmetic is at least one ester Substituent selected from the group consisting of an selected from the group consisting of a bronzer, a face pow C-C aliphatic ester, a functional C-C aliphatic ester, an der, an eye shadow, an eye liner, a mascara, a blush, a brow aromatic ester, a Substituted aromatic ester, any derivative powder, a baby powder, a lip gloss, and a lipstick; thereof, and any combination thereof; Element 12: wherein the ester derivative comprises at least one inorganic ester 0114 F. an agricultural product comprising a polysaccha Substituent selected from the group consisting of hypochlo ride ester microsphere according to Embodiment D option rite, chlorite, chlorate, perchlorate, Sulfite, Sulfate, a Sul ally including the corresponding Elements (or produced by a fonate, fluorosulfate, nitrite, nitrate, phosphite, phosphate, method of Embodiments A-C optionally including the corre phosphonates, borate, any derivative thereof, and any combi sponding Elements) dispersed in a fluid, wherein the polysac nation thereof; and Element 15: whereinforming the plurality charide ester microsphere further comprises at least one of polysaccharide ester microspheres involves spraying the selected from the group consisting of a herbicide, a fungicide, polysaccharide ester dope into a coagulation bath comprising an insecticide, a bactericide, a nitrogen source, a growth a non-solvent of the polysaccharide ester. Exemplary combi promoter, and any combination thereof; nations of embodiments may include, but are not limited to, 0115 G. a cigarette filter that comprises a filter material one of Elements 8-10 in combination with Element 11; one of and the polysaccharide ester microsphere according to Elements 8-10 in combination with Element 12: Element 11 Embodiment D optionally including the corresponding Ele in combination with Element 12; and Element 15 in combi ments (or produced by a method of Embodiments A-C nation with any of the foregoing. optionally including the corresponding Elements) dispersed 0111 Exemplary embodiment D disclosed herein therein; includes: a microsphere that includes a starch ester and hav 0116. H. a cigarette filter that comprises a filter material ing a hollow core and a wall. Optionally, at least one of the and a cavity or capsule therein, wherein the polysaccharide following elements may be included in the composition: Ele ester microsphere of Embodiment G is contained in the cavity ment 16: wherein the starch ester comprises at least one or capsule; and US 2014/0113826 A1 Apr. 24, 2014

0117 I. a food product that comprises a polysaccharide Example 4 ester microsphere according to Embodiment D optionally including the corresponding Elements (or produced by a I0122) Cellulose diacetate microspheres were analyzed for method of Embodiments A-C optionally including the corre fragrance release and compared to a polyethyleneloaded with sponding Elements) that further comprises at least one of a the same fragrance. The fragrance used was CITRUS 20627 flavorant, an aroma, a food agent, and a nutritional Supple (available from International Flavors & Fragrances). The ment. microspheres were loaded to about 25% by weight with the 0118. To facilitate a better understanding of the present fragrance, approximately that of the polyethylene loaded invention, the following examples of preferred or representa sample. Fragrance release was measured by weight loss. The tive embodiments are given. In no way should the following results indicated that the fragrance released faster from the examples be read to limit, or to define, the scope of the microspheres than the polyethylene, which may be due to the invention. porous nature and higher Surface area of the microspheres. As shown in FIG. 2, the microspheres released about 70% of the EXAMPLES CITRUS 20627 in the first 8-10 hours, while the polyethyl ene, over the same time period, released about 30%. Over the Example 1 next 70 hours, the microspheres continued a slow release of 0119 Cellulose diacetate microspheres loaded with Acid fragrance to about 80% released, and the polyethylene con Blue 290 were prepared by including Acid Blue 290 in the tinued on a moderate release rate profile reaching about 60% dope used to produce the microspheres where the weight ratio release in the same time frame. of cellulose diacetate to Acid Blue 290 was about 9:2. The loaded microspheres were soaked in water, which was ana Example 5 lyzed via spectroscopic techniques to determine the concen tration of Acid Blue 290 released from the loaded micro spheres and consequently a release rate. The average release I0123 Flake of cellulose diacetate with molecular weight rate was about 61 ppm dye/g of microspheres/hr. However, in of about 75,000 g/mol was used to form a dope in 90 wt % experiments where the grams of microspheres were increase acetic acid and 10 wt % water with a solids content of about with the same volume of water, the concentration of the dye 9 wt %. The dope was sprayed an anti-bearding fluid nozzle released into the water did not increase as expected, i.e., twice and "/43 air cap (available from Spraying Systems Co.) into a as many microspheres did not yield twice the concentration of 43.5 L coagulation bath of deionized water containing 110 dye in the water. Without being limited by theory, it is mL TWEEN 80 (a polyethylene sorbitol ester surfactant, believed that additives that are soluble in or have an affinity available from Sigma-Aldrich) and 10 mL SIGMA ANTI for the microsphere compositions (e.g., cellulose diacetate) FOAM B (an aqueous silicone emulsion, available from and the Surrounding environment (e.g., water) can reach an Sigma-Aldrich) was at room temperature and about 115 cm to equilibrium under static conditions. about 155 cm from the nozzle to produce microspheres. 0.124. The resultant microspheres were analyzed for par Example 2 ticle size via a sieve method (CA-MS2 only) (Table 1); par ticle size via a light scattering method using a Malvern Instru 0120 Never dried cellulose diacetate microspheres pre ment Model 2000 (Table 2); surface area, total pore volume, pared from a 90% acetic acid/10% water solvent and a room and average pore size via a BET method using a Micrometrics temperature precipitation bath were solvent exchanged with ASAP 2020 Accelerated Surface Area and Porosimetry Sys methanol. The microspheres were filtered and placed wet in tem (Table 3); and morphology via Scanning electron micros an ibuprofen/methanol solution for 20.5 hours under agitation copy (“SEM) (FIGS. 3-5). at room temperature. The microspheres were filtered and air dried at room temperature. This method produced micro TABLE 1 spheres with a 62.6% by weight loading of ibuprofen. The ibuprofen loaded microspheres were packed in a column. (CA-MS2) Water was flowed through the column at about 10-12 mL/min, and the effluent was analyzed for ibuprofen concen Sieve Size Approx. Microns % by Wt tration. The loaded microspheres released the ibuprofen ini #60 >250 4.7 tially quickly, like a “burst release for approximately the i8O 18O-2SO 15.9 #1 OO 1SO-18O 21.9 first 30-45 minutes and then begins to level off, perhaps with i140 106-1SO 29.3 a slow decline over time, to a rate of about 0.6-0.8 mg/min. #230 63-106 23.4 catch pan <63 4.8 Example 3 0121 Cellulose diacetate microspheres were tested for absorption of limonin from navel orange juice, the compo TABLE 2 nent of navel orange juice that make is bitter. Hydrated micro spheres (microsphere having be soaked in water to replace air Sample Do (microns) Dso (microns) Doo (microns) in the Void spaces) were added to samples of navel orange CA-MS1 59.4 131.9 257.9 CA-MS2 65.7 142.2 281.8 juice (about 2 g dry weight microspheres to 100 mL of navel CA-MS3 72.7 1619 3.19.3 orange juice), agitated for 1 hour, and then removed with a CA-MS4 27.8 109.5 396.9 wire mesh. The microspheres absorbed about 80% of the limonin in the navel orange juice. US 2014/0113826 A1 Apr. 24, 2014 22

TABLE 3 spherical, though not as uniform as the microspheres of Example 5. Similar to the microspheres of Example 5, these BET Surface Total Pore Average Pore Size microspheres have a hollow center and walls similar in thick Sample Area (m/g) Volume (mL/g) (angstroms) ness. However, these microspheres have less dense, more CA-MS1 12.3 O.074 239 porous walls as compared to the microspheres of Example 5. CA-MS2 12.6 0.077 246 FIG. 7 provides a higher resolution SEM micrograph of the CA-MS3 16.8 O.109 259 Surface of a microsphere that shows Smoother Surface than the microspheres of Example 5 but with more visible porosity. 0125 FIG. 3 provides an SEM micrograph of several I0129. This example demonstrates that polysaccharide microspheres from the CA-MS3 sample. The microspheres ester microspheres may be formed directly from polysaccha are substantially spherical. FIG. 4 provides a higher resolu ride ester product, which reduces capital costs, operating tion SEM micrograph of the surface of a microsphere that costs, and manufacturing time. Further, this example illus shows a rippled or crinkled surface with no significant visible trates that the morphology, porosity, and, consequently, porosity. FIG. 5 provides a higher resolution SEM micro release rates of the polysaccharide ester microspheres may be graph of the cross-section of a microsphere that shows hollow altered with the inclusion of salts in the polysaccharide ester interior and evidence of porosity in the walls of the micro dope. sphere. The walls of the microsphere are measured at about 40 microns to about 55 microns. Example 7 0.130 Starch diacetate in dried form (i.e., finished polysac Example 6 charide ester from FIG. 1) with molecular weight of about 0126 Cellulose diacetate from a cellulose acetate product 16,000 g/mol was used to form a dope in 90 wt % acetic acid (i.e., directly from polysaccharide ester synthesis 1.1 of FIG. and 10 wt % water with a solids content of about 35 wt %. 1 without finishing) with molecular weight of about 75,000 I0131 Microspheres were produced under the same con g/mol was diluted with water and acetic acid to yield a dope of ditions as Example 5 with a distance between the nozzle and 90 wt % acetic acid and 10 wt % water with a solids content the coagulation bath being about 63 cm to about 115 cm. The of about 9 wt %. No filtering was performed in the preparation resultant microspheres were analyzed for particle size via a of the dope. It should be noted that because filtration was not light scattering method (Table 7); surface area via a BET performed, the dope contains magnesium salts like magne method (Table 8); and morphology via SEM (FIGS. 8-9), sium sulfate and magnesium acetate. each as described above in Example 5. 0127. Microspheres were produced under the same con ditions as Example 5. The resultant microspheres were ana TABLE 7 lyzed for particle size via a sieve method (Table 4); particle size via a light scattering method (Table 5); Surface area via a Sample Do (microns) Dso (microns) Doo (microns) BET method (Table 6); and morphology via SEM (FIGS. SA-MS1 79.4 165.4 299.0 6-7), each as described above in Example 5.

TABLE 4 TABLE 8

% by Wt BET Surface Sieve Size Approx. Microns (CA-MS5) Sample Area (m/g) #60 >250 17.5 SA-MS1 1.13 i8O 18O-2SO 29.6 #100 1SO-18O 15.7 #140 106-1SO 20.8 #230 63-106 11.6 I0132 FIG. 8 provides an SEM micrograph of several catch pan <63 4.0 microspheres produced in this example. The microsphere product appears to contain starch acetate microspheres of two different sizes (i.e., a bimodal diameter distribution) that are substantially spherical and fibers. The larger of the spheres TABLE 5 are Smaller than the cellulose acetate microspheres of Sample Do (microns) Dso (microns) Doo (microns) Examples 5 and 6. FIG. 9 provides a higher resolution SEM micrograph of the cross-section of a microsphere that shows CA-MSS 46.0 126.3 249.O hollow interior and evidence of porosity in the walls of the microsphere, though the walls of the microsphere appear to be more dense than that of the cellulose acetate microspheres TABLE 6 of Examples 5 and 6. Further, in FIG. 9, the surface of adja cent microspheres indicates that the Surface of these starch BET Surface acetate microspheres is significantly smoother than that of the Sample Area (m/g) cellulose acetate microspheres of Examples 5 and 6. CA-MSS 23.7 Example 8 0128 FIG. 6 provides an SEM micrograph of several I0133) A dope comprising mixture by weight of starch microspheres produced in this example including a cross triacetate and cellulose diacetate was produced by mixing section of a microsphere. The microspheres are substantially equal volumes of a starch triacetate dope (about 35 wt % US 2014/0113826 A1 Apr. 24, 2014

solids in 90 wt % acetic acid and 10 wt % water) and a Example 11 cellulose diacetate dope (about 9 wt % solids in 90 wt % 0.139 Flake of cellulose diacetate with molecular weight acetic acid and 10 wt % water), thereby producing a dope of about 75,000 g/mol was used to form a dope in 90 wt % comprising about 80% starch triacetate and about 20% cel acetic acid and 10 wt % water with a solids content of about lulose diacetate each by weight of the total polysaccharide 9 wt %. Prior to cellulose diacetate flake addition, acesulfame ester. Microspheres were produced under the same conditions potassium (SUNNETTR) was fully dissolved in the acetic as Example 5 with a distance between the nozzle and the acid/water solvent at a solids content (cellulose diacetate coagulation bath being about 63 cm to about 115 cm. The weight basis) of about 200 wt %. The sweetener-loaded cel resultant microspheres were analyzed for morphology via lulose diacetate dope was sprayed via an anti-bearding fluid SEM (FIGS. 10-11). nozzle and 43 air cap into a 19 L coagulation bath of dena 0134 FIG. 10 provides an SEM micrograph of several tured ethanol at room temperature and about 89 cm from the microspheres in this example. The microsphere product nozzle to produce microspheres. appears to contain starch acetate microspheres with a broad 0140. The resultant microspheres were analyzed for par diameter distribution that are substantially spherical to ovu ticle size via a sieve method (Table 9). About 75 wt % of the lar. FIG. 10 provides a higher resolution SEM micrograph of microspheres are about 63 microns to about 150 microns, the cross-section of a microsphere that shows hollow interior which is smaller than the cellulose diacetate microspheres of and evidence of porosity in the walls of the microsphere with Example 5 that contain no acesulfame potassium where over a wall density between that of the cellulose acetate micro spheres of Examples 5 and 6 and the starch acetate micro 40 wt % are greater than about 150 microns. spheres of Example 7. Further, in FIG. 10, the surface the starch acetate/cellulose acetate microspheres is significantly TABLE 9 smoother than that of the cellulose acetate microspheres of Sieve Size Approx. Microns % by Wt Examples 5 and 6. #60 >250 4.7 i8O 18O-2SO 6.O Example 9 #1 OO 1SO-18O 10.3 i140 106-1SO 4S.O 0135 Flake of cellulose diacetate with a molecular weight #230 63-106 24.7 of about 75,000 g/mol was used to form a dope in 90 wt % catch pan <63 9.2 acetic acid and 10 wt % water with a solids content of about 9 wt %. Limonene flavor oil was dispersed in the dope using a rotor-stator homogenizer at greater than 15,000 rpm. Example 12 Limonene at 50%, 60%, and 70% loading levels was dis persed in the dope. The dope was sprayed via an anti-bearding 0141 Flake of cellulose diacetate with molecular weight fluid nozzle and "/43 air cap into a coagulation bath of deion of about 75,000 g/mol was used to form a dope in 90 wt % ized water containing TWEEN 80 and SIGMA ANTIFOAM acetic acid and 10 wt % water with a solids content of about Bat room temperature and located about 115 cm to about 155 9 wt %. Prior to cellulose diacetate flake addition, a straw cm from the nozzle to produce microspheres. berry oil flavor (Mother Murphy's Laboratories Flavor it 0.136 FIGS. 12-14 provide SEM micrographs of the 50%, TKO746) was fully dissolved in the acetic acid/water solvent 60%, and 70% limonene flavor oil loading levels, respec at a solids content (cellulose diacetate weight basis) of about tively. In each sample, the microspheres are substantially 100 with. The flavor-loaded cellulose diacetate dope was spherical and appear to be similar in structure to those of sprayed via an anti-bearding fluid nozzle and "/43 air cap into Example 5 (cellulose diacetate microspheres without a 43.5 L coagulation bath of deionized water containing 110 limonene). However, the size of the microspheres appears to mL TWEEN 80 and 10 mL SIGMA ANTIFOAMB at room be less than the Example 5 microspheres, or at least the temperature and about 89 cm from the nozzle to produce Volume fraction of smaller microspheres appears to be higher. microspheres. 0142. The cellulose diacetate microspheres produced Example 10 from the dope containing strawberry oil were, by visual inspection, similar to that of the cellulose diacetate micro 0.137 Flake of cellulose diacetate with molecular weight spheres of Example 5 (no additional flavorants) and the cel of about 75,000 g/mol was used to form a dope in 90 wt % lulose diacetate microspheres of Example 10 (with acetic acid and 10 wt % water with a solids content of about acesulfame potassium Sweetener). 9 wt %. Prior to cellulose diacetate flake addition, acesulfame 0143. Therefore, the present invention is well adapted to potassium (SUNNETTR), a high intensity sweetener, avail attain the ends and advantages mentioned as well as those that able from Celanese) was fully dissolved in the acetic acid/ are inherent therein. The particular embodiments disclosed water solvent at a solids content (cellulose diacetate weight above are illustrative only, as the present invention may be basis) of about 200 wt %. The sweetener-loaded cellulose modified and practiced in different but equivalent manners diacetate dope was sprayed via an anti-bearding fluid nozzle apparent to those skilled in the art having the benefit of the and /43 air cap into a 43.5 L coagulation bath of deionized teachings herein. Furthermore, no limitations are intended to water containing 110 mL TWEEN 80 and 10 mL SIGMA the details of construction or design herein shown, other than ANTIFOAMB at room temperature and about 89 cm from as described in the claims below. It is therefore evident that the nozzle to produce microspheres. the particular illustrative embodiments disclosed above may 0138 FIG. 15 provides an SEM micrograph of the result be altered, combined, or modified and all such variations are ant microspheres, which includes larger microspheres with a considered within the scope and spirit of the present inven Smoother Surface and Smaller microspheres with a Surface tion. The invention illustratively disclosed herein suitably that appears to be similar to those of Example 5. may be practiced in the absence of any element that is not US 2014/0113826 A1 Apr. 24, 2014 24 specifically disclosed herein and/or any optional element dis 9. A method comprising: closed herein. While compositions and methods are described forming a polysaccharide esterproduct from a polysaccha in terms of "comprising.” “containing,” or “including vari ride synthesis, wherein the polysaccharide ester product ous components or steps, the compositions and methods can comprises a starch ester and a solvent; also “consist essentially of or “consist of the various com producing a polysaccharide ester dope from the polysac ponents and steps. All numbers and ranges disclosed above charide ester product, wherein the polysaccharide ester may vary by Some amount. Whenever a numerical range with dope has a solids content of about 16% to about 50% by a lower limit and an upper limit is disclosed, any number and weight of the polysaccharide ester dope; and any included range falling within the range is specifically forming a plurality of polysaccharide ester microspheres disclosed. In particular, every range of values (of the form, from the polysaccharide ester dope. “from about a to about b,” or, equivalently, “from approxi 10. The method of claim 9, wherein the polysaccharide mately a to b,” or, equivalently, “from approximately a-b) ester product further comprises a cellulose ester. disclosed herein is to be understood to set forth every number 11. The method of claim 9 further comprising adding a and range encompassed within the broader range of values. cellulose ester to the polysaccharide ester dope. Also, the terms in the claims have their plain, ordinary mean 12. A method comprising: ing unless otherwise explicitly and clearly defined by the providing a finished polysaccharide ester product that patentee. Moreover, the indefinite articles “a” or “an,” as used comprises a starch ester, in the claims, are defined hereinto mean one or more than one producing a polysaccharide ester dope that comprises the of the element that it introduces. If there is any conflict in the finished polysaccharide ester product and a solvent, usages of a word or term in this specification and one or more wherein the polysaccharide ester dope has a Solids con patent or other documents that may be incorporated herein by tent of about 16% to about 50% by weight of the reference, the definitions that are consistent with this speci polysaccharide ester dope; and fication should be adopted. The invention claimed is: forming a plurality of polysaccharide ester microspheres 1. A method comprising: from the polysaccharide ester dope. forming a polysaccharide esterproduct from a polysaccha 13. The method of claim 12, wherein the polysaccharide ride synthesis, wherein the polysaccharide ester product ester dope further comprises a cellulose ester. comprises a polysaccharide ester and a solvent; 14. A microsphere comprising: diluting the polysaccharide ester product, thereby yielding a starch ester; and a polysaccharide ester dope; and having a hollow core and a wall. forming a plurality of polysaccharide ester microspheres 15. The microsphere of claim 14 further comprising a from the polysaccharide ester dope. cellulose ester. 2. The method of claim 1 further comprising: 16. The microsphere of claim 14, wherein the microsphere filtering the polysaccharide ester product before diluting. has a surface area of about 1 m/g to about 50 m/g as mea 3. The method of claim 1, wherein the polysaccharide ester sured by BET with nitrogen gas. comprises at least one ester derivative of at least one selected 17. A cosmetic comprising the polysaccharide ester micro from the group consisting of starch, cellulose, hemicellulose, sphere of claim 14 that further comprises at least one of an algenates, chitosan, and any combination thereof. aroma, a flavorant, and a colorant, wherein the cosmetic is at 4. The method of claim 3, wherein the ester derivative least one selected from the group consisting of a bronzer, a comprises at least one organic ester Substituent selected from face powder, an eye shadow, an eye liner, a mascara, a blush, the group consisting of an C-Coaliphatic ester, a functional a brow powder, a baby powder, a lip gloss, and a lipstick. C-C aliphatic ester, an aromatic ester, a Substituted aro 18. An agricultural product comprising a polysaccharide matic ester, any derivative thereof, and any combination ester microsphere of claim 4 dispersed in a fluid, wherein the thereof. polysaccharide ester microsphere further comprises at least 5. The method of claim 3, wherein the ester derivative one selected from the group consisting of a herbicide, a fun comprises at least one inorganic ester Substituent selected gicide, an insecticide, a bactericide, a nitrogen source, a from the group consisting of hypochlorite, chlorite, chlorate, growth promoter, and any combination thereof. perchlorate, Sulfite, Sulfate, a Sulfonate, fluorosulfate, nitrite, 19. A cigarette filter that comprises a filter material and the nitrate, phosphite, phosphate, phosphonates, borate, any polysaccharide ester microsphere of claim 14 dispersed derivative thereof, and any combination thereof. therein. 6. The method of claim 1, wherein the polysaccharide ester comprises at least one ester derivative of starch and at least 20. A cigarette filter that comprises a filter material and a one ester derivative of cellulose. cavity or capsule therein, wherein the polysaccharide ester 7. The method of claim 6, wherein the polysaccharide ester microsphere of claim 15 are contained in the cavity or cap dope has a solids content of about 4% to about 50% by weight Sule. of the polysaccharide ester dope. 21. A food product that comprises a polysaccharide ester 8. The method of claim 1, whereinforming the plurality of microsphere of claim 14 that further comprises at least one of polysaccharide ester microspheres involves spraying the a flavorant, an aroma, a food agent, and a nutritional Supple polysaccharide ester dope into a coagulation bath comprising ment. a non-solvent of the polysaccharide ester.