US 2010.0015184A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0015184A1 Tue (43) Pub. Date: Jan. 21, 2010

(54) METHODS OF MAKING PHARMACEUTICAL Publication Classification COMPONENTS FOR CUSTOMIZED DRUG PRODUCTS (51) Int. Cl. A6IR 9/00 (2006.01) (76) Inventor: Stephen M. Tuel, Columbia, SC (52) U.S. Cl...... 424/400 (US) (57) ABSTRACT Correspondence Address: Methods and systems for developing and manufacturing STPKALA LLC componentized drug product precursor modules that can be 5401 NETHERBYLANE, SUITE 102-A simply assembled to create customized drug products are NORTH CHARLESTON, SC 29420 (US) disclosed. Each module contains components of a final drug product (e.g., active pharmaceutical ingredients, nutritional (21) Appl. No.: 12/518,311 ingredients, and/or excipients) in a fixed mixture selected to maximize desired pharmaceutical characteristics (e.g., stabil (22) PCT Fled: Dec. 13, 2007 ity, manufacturing efficiency) and minimize cost. The mod ules can be extensively tested for quality and assembled immediately, or at a later time, in multiple combinations to (86) PCT NO.: PCT/US2007/025430 customize the final drug product characteristics (e.g., mul tiple active ingredients, doses, flavor, Viscosity, etc.) to meet S371 (c)(1), individual patient/consumer needs and/or preferences while (2), (4) Date: Jun. 9, 2009 assuring high quality. Permitted combinations may be main tained in a database to enable networked drug product selec Related U.S. Application Data tion, prescribing, and ordering. Each resulting customized (60) Provisional application No. 60/874,554, filed on Dec. drug product dose can be labeled to facilitate compliance and 13, 2006. reduce the number of drug products administered per day. Patent Application Publication Jan. 21, 2010 Sheet 1 of 7 US 2010/0015184 A1 Figure 1 AP module dose selection

Search public clinical, medical, and health literature, especially pediatric, geriatric, and metabolic disease areas

Defined minimum and maximum No License or Create additional doses, minimum escalation proprietary dose knowledge interval dose

Convert, as necessary, relative doSeS to absolute doses

Minimum dose is ultiple of escalation interva NO Analysis of clinical use, market Or ViceVersa demand, and total dosing range

Select greatest common factor or Smaller of minimum

Minimum dose dose and escalation interval is greater than escalation interval Select minimum dose as API module dose Select escalation interval as API module dose

N Broad total dosing range O Develop one API module dose

YeS manufacturingMarket and analysis Develop two API module doses Patent Application Publication Jan. 21, 2010 Sheet 2 of 7 US 2010/0015184 A1 Figure 2 API module excipient selection

N Liquid formulation O

Available public Available public or proprietary data on API gr proprietary data on granulg solubility formulation

License/create additional

formulation knowledge

Add Solubilizers, Develop simplified antioxidants, pH modifiers coated granules;

only if absolutely necessary

binder

it sustained release characteristics

Avoid flavors, Sweeteners, Colors, or viscosity agents Minimize granule size

Use aseptic process to avoid /preservatives

Minimize liquid volume

Goal is minimum number of excipients Patent Application Publication Jan. 21, 2010 Sheet 3 of 7 US 2010/0015184 A1

Figure 3 Excipient module component selection Liquid formulation N

YeS

Taste-masking module N Compare volumes of Solid dose AP module portfolio with Select portfolio of sweet and non total Volumes of final Sweet flavors; add Sweeteners, other formulation options taste-masking agents as needed

Select limited

number of target Colorant module volumes for "filler modules

Develop limited number of color Com

ponents with maximum compatibility Select physical components of modules Viscosity module No

Develop limited number of viscosity agents with maximum compatibility

Develop limited number of preservative modules with maximum compatibility

Goal is minimum number of excipient modules with maximum flexibility of combinations Patent Application Publication Jan. 21, 2010 Sheet 4 of 7 US 2010/0015184A1

Figure 4 Module portfolio management Potential new AP module

DOSe?cOncentration inside range of existing modules

Select dose Select (see Fig. 1) excipients ASSess analytical, (see Fig. 2) formulation, and manufacturing issues

Need for

new excipient module(s

Potential new excipient module Change in

Components alters need for new module(s

Select excipient module components (see Fig. 3)

Additional opportunities to use module

Change in Reassess market, Components creates new Opportunities business factors

Go/NoGo decision Patent Application Publication Jan. 21, 2010 Sheet 5 of 7 US 2010/0015184 A1

Figure 5 Module selection for final assembly

Select first API module type

Select number of AP modules Select next AP to provide a dose based on user's physical and clinical module type measures, age, species/breed, or other characteristics

Additional AP Liquid No needed formulation

Select compatible Select final Compatible taste-masking AP module product form and Yes available module(s) size, e.g., Capsule Select compatible Colorant, viscosity, Select number and/or preservative of excipient modules as needed (filler) modules

All needed modules available Forward need for additional

modules to R&D Assemble into final product or package for later assembly Patent Application Publication Jan. 21, 2010 Sheet 6 of 7 US 2010/0015184 A1

Figure 6 Final assembly options

AP Excipient module module portfolio portfolio

Modules for final product

Consumer assembly assembly immediate assembly

Manual or Manual Or automated process automated process

Patent Application Publication Jan. 21, 2010 Sheet 7 of 7 US 2010/0015184 A1

Figure 7 Quality control and ordering processes

Public chemical, pharma Ceutical, medical, an veterinary information Module design

Batch manufacturing 1N License/Create

of modules proprietary ga information Quality and

stability testing

Module assembly Permitted Combinations database/ordering application

Physician, Veterinarian, or Other health professional US 2010/00151.84 A1 Jan. 21, 2010

METHODS OF MAKING PHARMACEUTICAL 0007. In some embodiments, the present invention COMPONENTS FOR CUSTOMZED DRUG includes a method and system for developing and manufac PRODUCTS turing componentized drug product precursor modules that can be simply assembled to create customized drug products. CROSS REFERENCE TO RELATED Some precursor modules of the present system contain two or APPLICATIONS more components of a final drug product in a fixed mixture selected to maximize desired pharmaceutical characteristics 0001. This application claims benefit of priority under and minimize cost. The modules are divided into two classes: PCT Chapter I, Article 8, and 35 U.S.C. S 119(e) of U.S. 1) modules containing an active pharmaceutical ingredient or Provisional Application No. 60/874,554, entitled “Method of specific nutritional ingredient (hereafter called API), and 2) Making Pharmaceutical Components for Assembly of Cus modules containing only excipients. tomized Drug Products.” filed on Dec. 13, 2006, which is 0008. The modules can be extensively tested for quality incorporated herein by reference. and assembled in multiple predetermined combinations, cus tomizing the final drug product characteristics to meet TECHNICAL FIELD patient/consumer needs and/or preferences while assuring 0002 This invention relates to methods and systems for high quality. Permitted combinations can be maintained in an developing and manufacturing componentized drug product Internet-linkable computer database to enable networked precursor modules that can be assembled to create custom drug product selection, prescribing, and ordering. The result ized drug products. ing customized drug product can facilitate compliance and reduce the number of drug products administered per day. BACKGROUND ART 0009. Some embodiments of the present invention provide an API module, comprising: at least one excipient in a first 0003 Pharmaceutical products for use in humans or ani fixed amount, and at least one active pharmaceutical ingredi mals are produced primarily in two ways. High Volume or ent in a second fixed amount of at least a dose escalation high priced drugs are manufactured under very tightly con interval or a fraction thereof. In other embodiments, the sec trolled conditions with detailed specifications, quality test ond fixed amount can be greater than the dose escalation ing, and documentation. Because of the high cost and com interval. In still other embodiments, the second fixed amount plexity of this type of pharmaceutical manufacturing, low can be less than a dose of the at least one active pharmaceu Volume, highly specialized drugs are produced in a cottage tical ingredient. Additional embodiments provide the second industry of compounding pharmacies. These pharmacies mix fixed amount being less than the minimum dose of the at least various active ingredients and excipients into an often unique one active pharmaceutical ingredient. In yet other embodi product based on a doctor's prescription. The specifications, ments, methods for making at least one API module are quality testing, and documentation are often minimal or non provided. Such methods comprise, in some embodiments, existent. Fully testing these products for quality can be cost isolating a first fixed amount of a first API, combining the first prohibitive because of the small volume. Patients are often fixed amount of the first API with a second fixed amount of at forced to choose between the assurance of high quality and least one first excipient, to form the at least one API module. the flexibility of customized products. When patients are 0010 Further embodiments provide an excipient module, unable to obtain high quality customized drug products they comprising: at least one first excipient in a first fixed amount; often demonstrate lower compliance with the prescribed regi and at least one second excipient in a second fixed amount; men and can Suffer health consequences. wherein the at least one first excipient and the at least one 0004 Processes of preparation and manufacturing of spe second excipient are compatible with at least one active phar cific active ingredients, including the use of specific excipi maceutical ingredient. In some embodiments, the Sum of the ents in the formulation, are known. These cover only a frac first fixed amount and the second fixed amount is sufficient to tion, however, of the millions of possible combinations of active and inactive ingredients which can address special format least one final drug product comprising the at least one needs of patient groups. Various compounding machines active pharmaceutical ingredient. In other embodiments, the related to this area are also known, but these merely automate at least one first excipient and the at least one second excipient the traditional process of mixing bulk actives with a series of are compatible with two or more active pharmaceutical ingre excipients according to a recipe. They do little to address the dients. quality issues inherent in the compounding of . 0011 Still further embodiments provide a final drug prod 0005 Accordingly, there exists a need for a method and uct, made by a process comprising: combining at least one system for developing and manufacturing componentized API module comprising at least one active pharmaceutical ingredient, and at least one excipient module, to make the drug product precursor modules that can be simply assembled final drug product; wherein the at least one active pharma to create customized drug products. ceutical ingredient is present in the final drug product in an amount effective for treating at least one disease, at least one DISCLOSURE OF THE INVENTION disorder, at least one condition, or a combination thereof, in at 0006. The following presents a simplified summary of the least one human or animal patient in need thereof. invention in order to provide a basic understanding of some 0012 Yet other embodiments provide a method for manu aspects of the invention. This Summary is not an extensive facturing a final drug product, comprising: selecting a first overview of the invention. It is not intended to identify key or API module comprising at least one first active pharmaceu critical elements of the invention or to delineate the scope of tical ingredient and at least one first excipient; determining a the invention. Its sole purpose is to present concepts of the number of the first API module; choosing a first excipient invention in a simplified form as a prelude to the more module comprising at least one second excipient; determin detailed description that is presented later. ing a number of the first excipient module; and combining the US 2010/00151.84 A1 Jan. 21, 2010

number of the first API module and the number of the first nents implementable in a system operable to manufacture at excipient module to manufacture the final drug product. least one final drug product, at least one final drug package, or 0013 Some embodiments of the present invention further both, comprising: a computer-executable component for pro comprise: selecting a second API module comprising at least viding one or more of compatibility information, dose infor one second active pharmaceutical ingredient and at least one mation, and dose escalation interval information for at least third excipient; determining a number of the second API one API module in the API module portfolio. Other embodi module, optionally choosing a second excipient module com ments provide Such computer-readable medium as a separate prising at least one fourth excipient, and determining a num embodiment. ber of the second excipient module; and combining the num 0019. Further embodiments provide an excipient module ber of the second API module and optionally the number of portfolio, comprising a plurality of different excipient mod the second excipient module with the number of the first API ules. Such embodiments optionally include one or more com module and the number of the first excipient module to manu puter-executable components for providing compatibility facture the final drug product. information for one or more excipient module in the excipient 0014 Some embodiments of the present invention provide module portfolio. Other embodiments provide such com methods of manufacturing at least one final drug product, at puter-readable medium as a separate embodiment. least one final drug package, or both, implemented by com 0020. Other embodiments provide methods for develop puter-executable instructions stored on one or more com ing an API moduleportfolio. Still other embodiments provide puter-readable media. methods for developing an excipient module portfolio. 0015 Still other embodiments provide a final drug pack 0021. Other features and advantages of the present inven age, comprising: at least one API module, which comprises at tion will be apparent to those skilled in the art from a careful least one first excipient, and at least one active pharmaceutical reading of the entire application, including the Modes for ingredient; and at least one excipient module, which com Carrying Out the Invention presented below and accompa prises at least one second excipient; wherein the at least one nied by the drawings. second excipient is compatible with the at least one active pharmaceutical ingredient, wherein the at least one active BRIEF DESCRIPTION OF DRAWINGS pharmaceutical ingredient is present in the final drug package 0022 FIG. 1 shows a process for selection of an API in an amount effective for treating at least one disease, at least module dose according to one embodiment of the present one disorder, at least one condition, or a combination thereof, invention; in at least one human or animal patient in need thereof; and 0023 FIG. 2 shows a process for minimizing the number wherein the at least one API module and the at least one of excipients in an API module according to one embodiment excipient module are adapted to form a final drug product. of the present invention; 0016 Some embodiments provide a system for manufac 0024 FIG.3 shows a process for developing a portfolio of turing at least one final drug product, at least one final drug and selecting the components in, modules not containing an package, or both, comprising: at least one API module port API according to one embodiment of the present invention; folio comprising a plurality of different API modules; and at 0025 FIG. 4 shows a process for managing the portfolio of least one excipient module portfolio comprising a plurality of modules according to one embodiment of the present inven different excipient modules; wherein the at least one API tion; module portfolio and the at least one excipient module port 0026 FIG. 5 shows a process for selecting modules for folio are operatively connected to manufacture the at least one final drug assembly according to one embodiment of the final drug product, the at least one final drug package, or both. present invention; Other embodiments further comprise one or more means for 0027 FIG. 6 shows a process including alternative steps storing compatibility information for each API module and for assembling modules for the final drug product according each excipient module. to one embodiment of the present invention; 0017 Additional embodiments provide a computer-read 0028 FIG. 7 shows a method for controlling quality, able medium having computer executable components including assessing compatibility and permissible combina implementable in a system operable to manufacture at least one final drug product, at least one final drug package, or tions of modules, and ordering processes according to one both, comprising: a computer-executable component for pro embodiment of the present invention. viding one or more of compatibility information, dose infor MODES FOR CARRYING OUT THE INVENTION mation, and dose escalation interval information for at least one API module in an API module portfolio; and a computer 0029 API module' indicates an isolated first fixed executable component for providing compatibility informa amount of at least one active pharmaceutical ingredient tion for at least one excipient module in an excipient module together with a second fixed amount of at least one excipient. portfolio. In some embodiments, compatibility information In certain embodiments, the at least one excipient is compat for an API module indicates compatibility with one or more of ible with the at least one API. The API module may be other APIs, other API modules, excipients, and excipient enclosed in any suitable container, for example, so that the modules. In still other embodiments, compatibility informa module may be stored for a period of time before being tion for an excipient module indicates compatibility with one combined with one or more other modules to form a final drug or more of APIs, API modules, other excipients, and other product. Suitable containers include, but are not limited to, excipient modules. vials, ampules, capsules, pipettes, packets such as foil pack 0018 Still other embodiments provide an API module ets, bubble packets, and the like; and those containers may be portfolio, comprising a plurality of different API modules. water soluble, soluble in another solvent, insoluble, biode Such embodiments optionally include a computer-readable gradable, edible, recyclable, reusable, sterilizable, dispos medium having one or more computer executable compo able, or combinations thereof. Such containers can be made US 2010/00151.84 A1 Jan. 21, 2010

of any suitable material. Such as, for example, glass, metal, excipient in a second fixed amount effective to carry, solubi ceramic, polymer, paper, cardboard, and combinations lize, suspend, bind, and/or stabilize the first excipient in the thereof. In some embodiments, an API module is not enclosed first fixed amount. Excipient modules may contain two or in a container; in such embodiments, the API module could be more excipients for any Suitable purpose in any Suitable in the form of a pill, pellet, frozen pellet, single granule, or the amounts. In some embodiments, those Suitable amounts do like. The first fixed amount of the at least one API in an API not exceed amounts needed to form the maximum dose of an module is any suitable amount, and is known or is determin API, or the maximum safe amount of an API inadministrable able. In some embodiments, the first fixed amount is equal to form. In other embodiments, those Suitable amounts are frac the dose escalation interval for the API, the minimum dose for tions of the amounts sufficient to carry, Solubilize, Suspend, the API, or both when those amounts are equal. In other bind, and/or stabilize a dose of an API, and/or impart at least embodiments, the first fixed amount is a fraction of the dose one characteristic to a final drug product. Those Suitable escalation interval or the minimum dose. In still other amounts can be chosen from amounts suitable for a minimum embodiments, the first fixed amount is an amount other than dose of an API, a dose escalation interval for an API, or a the dose escalation interval, the minimum dose, or a fraction fraction of either of the foregoing, in some embodiments. thereof. For example, the first fixed amount could be a mul 0031 “API module portfolio” refers to a plurality of dif tiple of the minimum dose or the dose escalation interval, or ferent API modules. In some embodiments, information it could be any other Suitable amount. In some embodiments, about one or more API modules is available for the API the first fixed amount does not exceed the maximum dose of module portfolio. Such information includes any suitable the API. In other embodiments, the first fixed amount does not information, and may comprise one or more of identity, exceed the maximum safe amount of the API. In still other amount, co-API compatibility, excipient compatibility, co embodiments, the first fixed amount does not exceed about compatibility (for APIs administered separately), 80%, about 50%, about 25%, or about 10% of the minimum allergy and adverse drug reaction information, minimum dose of the API. The second fixed amount of the at least one dose, dose escalation interval, dosing schedule, and maxi excipient is any suitable amount. In some embodiments, the mum dose for each API in each API module. second fixed amount is an amount Sufficient to carry, solubi 0032) “Excipient module portfolio” indicates a plurality lize, suspend, bind, and/or stabilize the first fixed amount of of different excipient modules. In some embodiments, infor the at least one API, and/or impart at least one characteristic mation about one or more excipient modules is available for to a final drug product. In still other embodiments, an API the excipient module portfolio. Such information includes module optionally contains at least one second API in a third any suitable information, and may comprise one or more of fixed amount. In further embodiments, an API module con identity, amount, API compatibility, co-excipient compatibil tains at least one second excipient in a fourth fixed amount. ity, allergy information, minimum effective excipient The concept of the fixed amount allows for degradation of a amounts, maximum recommended excipient amounts, dos given ingredient that may occur over time in Some embodi age form information, timed-release information, and the like mentS. for each excipient in each excipient module in the portfolio. 0030 “Excipient module’ indicates an isolated first fixed 0033 “Final drug package” means a collection of one or amount of at least one excipient. The first fixed amount can be more API modules and one or more excipient modules suffi any suitable amount. In some embodiments, the first fixed cient to formulate a final drug product. In some embodiments, amount is known or is determinable. In other embodiments, a final drug package is adapted to be provided to a treating the first fixed amount is a Sufficient amount, that is, an amount medical professional and/or a patient so the professional or Sufficient to carry, Solubilize, Suspend, bind, and/or stabilize a patient can formulate the final drug product. In further given amount of at least one API and/or at least one other embodiments, a final drug package is sufficient to formulate a excipient, and/or impart at least one characteristic to a final single dose. In still further embodiments, a final drug package drug product. The excipient module can comprise a container, is Sufficient to independently formulate more than one single in Some embodiments, such as those containers described for dose. For example, a final drug package in some embodi API modules. In other embodiments, an excipient module ments contains enough modules and optionally instructions comprises a first fixed amount of a first excipient, and a to formulate a month's worth of daily single doses. A final second fixed amount of a second excipient. The first fixed drug package, in certain embodiments, is not in a form amount and the second fixed amount are, independently, any intended for administration directly to the patient. suitable amounts. In some embodiments, the first fixed 0034 “Final drug product” means, in some embodiments, amount and the second fixed amount together are sufficient to a combination of the contents of at least one API module and carry, solubilize, Suspend, bind, and/or stabilize a given at least one excipient module in a form that can be adminis amount of an API, and/or impart at least one characteristic to tered to a human or animal patient. In some embodiments, a a final drug product. In other embodiments, the first fixed final drug product contains one dose of at least one API, and amount and the second fixed amount together are sufficient to a Sufficient amount of at least one excipient. In other embodi carry, Solubilize, Suspend, bind, and/or stabilize various ments, a final drug product comprises the contents of at least amounts of more than one API, and/or impart at least one one API module and two or more alike or different excipient characteristic to a final drug product. In still other embodi modules. In still other embodiments, a final drug product ments, the first fixed amount is sufficient to carry, solubilize, comprises the contents of two or more alike or different API Suspend, bind, and/or stabilize a given amount of a first API. modules and two or more alike or different excipient mod while the second fixed amount is sufficient to carry, solubi ules. lize, Suspend, bind, and/or stabilize another given amount of 0035. In those embodiments in which “the excipients are a second API. Instill other embodiments, an excipient module the same or different,” that means, for example, that a first comprises a first excipient in a first fixed amount effective to excipient can be the same as, or different from, a second impart a characteristic to a final drug product, and a second excipient. If there are more than two excipients, any one US 2010/00151.84 A1 Jan. 21, 2010 excipient may be the same as or different from any other grams per kilogram or square meter respectively. In these excipient. For example, a first excipient may be the same as a cases, the dose recommendation must be converted into an second excipient, both of which differ from a third excipient. absolute measure by evaluating the applicable characteristic Alternatively, all three excipients in the previous example can of the patient population using the particular API. For differ from each other. The amount of any excipient in one example, an API given to adolescents for hormonal regulation module is independent of whether the excipient is the same as during puberty is unlikely to be used inapatient weighing less or different from any other excipient in another module. than 30 kg. If the relative minimum dose is 8 mg/kg and the 0036 “Combining the number of modules refers to com dose escalation interval is 2 mg/kg, then the absolute mini bining the contents of the modules, which are present in any mum dose would be 240 mg and the dose escalation interval Suitable number, in any suitable manner. The modules could would be 60 mg. An API with identical relative dose recom be mixed together, and their biodegradable or edible contain mendations (8 mg/kg and 2 mg/kg respectively) that is used ers are mixed in with the contents of the modules, in some for life Support in premature infants (who can weight only embodiments. In other embodiments, the contents of the hundreds of grams) would have much smaller absolute dose modules are removed from the containers and mixed together. recommendations at 4 mg and 1 mg for the minimum and In certain embodiments, the contents of the modules are escalation interval respectively. In some embodiments, a quantitatively transferred for mixing. In still other embodi “dose' is an amount of an API effective for treating at least ments, the contents of some modules could be added to the one disease, at least one disorder, at least one condition, or a contents of other modules, in the containers of those other combination thereof. In other embodiments, a "dose' is an modules. established amount of an API. Such as, for example, a recom 0037 “Manufacture' can indicate any suitable steps for mended daily allowance. making an article. Manufacturing can take place in a factory, 0041. Once absolute minimum and maximum dose, and in a specially-adapted apparatus such as a kiosk, a portable minimum dose escalation interval are established, the dose of kit, and a machine, and in a patient's home. For example, a the API within the module is selected. In some embodiments, patient can manufacture a final drug product from a final drug the minimum dose is either equal to, or is a whole number package by combining a number of alike or different API multiple of the dose escalation interval, e.g., for a dose esca modules and a number of alike or different excipient modules lation interval of 5 mg. the minimum dose is usually 5 mg. or to form the final drug product. 10 mg. or 15 mg, etc. Also, in Some cases, the minimum 0038. The present invention provides, in some embodi escalation interval is less than the minimum dose and all ments, a method and system for developing and manufactur generally prescribed doses will be a whole number multiple ing componentized drug product precursor modules. The of the dose escalation interval. Thus, in some API modules, modules are divided into two classes: 1) modules containing the dose in a single module is equal to the minimum dose an active pharmaceutical ingredient or specific nutritional escalation interval. ingredient (API), and 2) modules containing only excipients. 0042. In the event that the dose escalation interval is The development process differs for each class. greater than the minimum recommended dose, the minimum recommended dose may be selected for the dose within the Modules Containing an API API module if the dose escalation interval is a whole number 0039. Some issues that govern the development of mod multiple of that minimum dose (e.g., for a minimum dose of ules that contain an API include selecting the dose and mini 10 mg, and a dose escalation interval of 20 mg. or 30 mg, etc.). mizing the number of excipients. FIG. 1 illustrates and sum 0043. Another potential circumstance is where the mini marizes the process of selecting the dose of an API in the mum dose is not a whole number multiple of the dose esca module, in one embodiment of the invention. One possible lation interval, e.g., a minimum dose of 5 mg with a dose step in determining the dose of an API module is to assess the escalation interval of 2 mg. In this case a judgment must be range of doses prescribed and/or used for that particular API. made whether to use the greatest common factor of the mini Drug formularies and FDA records may provide information mum dose and escalation interval (e.g., 1 mg in the previous on currently manufactured APIs, in some embodiments. In example), or to proceed with the Smaller of the minimum dose other embodiments, recommended minimum and maximum and escalation interval (2 mg in the previous example) and doses, and minimum dose escalation intervals, can be deter force prescribing clinicians and/or consumers to choose mined through a detailed assessment of the clinical, medical, between a dose somewhat higher or lower than the recom and health literature by methods known in the art. Searches mended minimum (e.g., 4 mg or 6 mg in the previous need not be limited to specific diseases, conditions, or indi example), or to choose another amount. This decision may cations, but may include all potential uses, both regulatory rely on a broad analysis of clinical usage (e.g., physicians approved and unapproved. Searches for minimum dose and may prefer the Somewhat lower minimum dose), market dose escalation interval may focus on literature discussing demand (e.g., the percentage of patients actually using the pediatric, geriatric, and metabolic disease (e.g., hepatic insuf minimum dose may be insignificant; in the previous example ficiency) because these populations are often more fragile and every patient may be receiving 10 mg or above), and total require greater accuracy in dosing. In cases where the public dosing range (i.e., Smaller modular dose is more practical for literature is insufficient, it may be necessary to license or a narrow total range, as will be discussed below). otherwise obtain existing proprietary knowledge or to create 0044 Another API dose selection decision is whether to proprietary knowledge through clinical trial methods known develop an additional dose module. Such as, for example, an in the art. API module having a higher dose of the API. In drugs with a 0040 Dose recommendations are often given in terms broad total range (maximum dose minus minimum dose), the relative to patient characteristics, especially in pediatric maximum dose can be a very large multiple of the minimum patients, e.g., a dose may be relative to the patient's weight or dose or escalation interval. This can require a large number of body Surface area and recommended as a number of milli API modules, e.g., a drug with a minimum dose/escalation US 2010/00151.84 A1 Jan. 21, 2010

interval of 5 mg, yielding an API module dose of 5 mg, would lites, stereoisomers, enantiomers, diastereomers, salts, Sol require 100 modules to reach a maximum dose of 500 mg. For Vates, hydrates, complexes, polymorphs, crystals, co-crys some embodiments, a large number of API modules may be tals, and other chemical- and physical derivatives of considered inconvenient. In these cases one or more higher pharmacologically-active Substances. dose modules can be developed. The exact dose multiple of 0048 Moreover, it is understood that some substances the initial module may depend on market and manufacturing may be considered active, and may also find use as an excipi analysis, but a 10x multiple is a useful default option for some ent. For example, certain antibiotics could be useful as APIs embodiments. in some embodiments of the present invention, while they 0045 FIG. 2 summarizes the process of minimizing the also could find use as preservative excipients in other embodi number of excipients in an API module, in one embodiment. ments of the present invention. Indeed, some ingredients After the dose of an API module has been selected, the next could function simultaneously as both APIs and excipients. step can be to choose one or more additional components to For further examples, alcohol and mineral oil can be used as carry and stabilize the active ingredient within the module. APIs or as excipients. One of ordinary skill in the art will For some embodiments such as solid formulations, this may appreciate that describing a substance as a member of one be a relatively straightforward process of encapsulating very class (e.g., API) does not preclude using that Substance in the small amounts of the API, with or without a binder, in a other class (e.g., excipient), and vice versa. water-soluble coating, with or without Sustained release char 0049 Active pharmaceutical ingredients suitable for API acteristics, using methods known in the art to create granules modules include, but are not limited to, analgesics and muscle Such as those used to fill capsules. The granule size may be relaxants, anesthetics and Surgical adjuvants, antibiotics, minimized to permit the greatest number of potential combi antidiabetic agents, antifungal agents, antihistamines, anti nations during final assembly of the final drug product. inflammatory agents, antimicrobial agents, antiparasitic 0046 For some embodiments comprising liquid formula agents, antivirals, biological and cellular agents, bone disease tions, the process may start with the selection of a solvent or agents, botanicals, cardiovascular agents, dermatologic Suspending agent to create a liquid. A liquid formulation may agents, diuretics, gastrointestinal agents, hematologic and be in any suitable form, such as Solution, Suspension, slurry, oncologic agents, hormones, minerals, neuromodulators, or the like. Some liquid formulation API modules of the nutraceuticals, obstetric and fertility agents, opthalmologic present invention provide formulary simplicity. In certain agents, proteins, enzymes and enzyme inhibitors, respiratory embodiments, an API module has only an active ingredient agents, rheumatologic agents, Steroids, urological agents, and a solvent; whenever possible additional excipients may vitamins, and other agents. be avoided. Antioxidants, acidifiers, alkalinizers, and buffers 0050 Suitable analgesics and muscle relaxants include, may be required, but for an API module, no flavors, sweeten but are not limited to, acetaminophen, alfentanil, almotriptan, ers or taste-masking agents, colors, or viscosity agents are aspirin, bromfenac, buprenorphine, butalbital, butorphanol, needed in Some embodiments. Preservatives and antiseptics carisoprodol, chlorZoxaZone, codeine, cyclobenzaprine, dan are permitted, but can be avoided by using an aseptic manu trolene, dihydrocodeine, dihydroergotamine, eletriptan, facturing process. Minimizing the number of excipients may ergotamine, fentanyl, froVatriptan, hydrocodone, hydromor simplify analytic method development and manufacturing phone, levorphanol, meclofenamate, meprobamate, meperi development and expense, and likely promotes a more stable dine, metaxalone, methadone, methocarbamol, morphine, formulation. Based on these and/or other considerations, the nabilone, nalbuphine, naratriptan, pentazocine, formula is developed by methods known in the art. The vol orphenadrine, oxycodone, oxymorphone, propoxyphene, ume of liquid can be minimized to permit the greatest number remifentanil, rizatriptan, Sufentanil, Sumatriptan, tramadol, of potential combinations during assembly of the final drug Ziconotide, and Zolmitriptan. product. 0051 Suitable anesthetics and surgical adjuvants include, 0047 APIs may be chosen from any suitable active phar but are not limited to, articaine, atracurium, benzocaine, bupi maceutical ingredient. As used herein, “active pharmaceuti vacaine, chloroprocaine, cisatracurium, desflurane, dexme cal ingredient” refers very broadly to any Substance that may detomidine, dibucaine, enflurane, etomidate, glycopyrrolate, have pharmaceutical, nutritional, nutraceutical, or other isoflurane, ketamine, lidocaine, mepivacaine, metaraminol, activity in a human or animal body. Such substances need not methohexital, midazolam, pancuronium, prilocalne, require formal government approval. Such as FDA approval. procaine, proparacaine, propofol, rocuronium, ropivacaine, Substances that can be sold as dietary Supplements, such as sevoflurane, Succinylcholine, tetracaine, and vecuronium. Vitamins, minerals, botanicals, and the like are specifically 0.052 Suitable antibiotics include, but are not limited to, included within the scope of APIs. In some embodiments, an acetohydroxamic acid, amikacin, aminosalicylic acid, amox active pharmaceutical ingredient is any component of a final icillin, amplicillin, azithromycin, aztreonam, bacitracin, bleo drug product intended to furnish pharmacological activity or mycin, capreomycin, carbenicillin, cefaclor, cefadroxil, cefa other direct effect in the diagnosis, cure, mitigation, treat Zolin, cefdinir, cefditoren, cefepime, cefixime, cefoperaZone, ment, or prevention of disease, or to affect the structure or any cefotaxime, cefotetan, cefoxitin, cefpodoxime, cefprozil, function of the body of humans or other animals. Active ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, pharmaceutical ingredients include those components of the cefuroxime, cephalexin, chloramphenicol, ciprofloxacin, final drug product that may undergo chemical change during clarithromycin, clindamycin, cloxacillin, colistin, cyclos the manufacture of the final drug product and be present in the erine, dapsone, daptomycin, demeclocycline, dicloxacillin, final drug product in a modified form intended to furnish the doripenem, doxycycline, ertapenem, erythromycin, etham specified activity or effect. In some embodiments, active butol, ethionamide, fosfomycin, gemifloxacin, gentamicin, pharmaceutical ingredients include Substances that affect the gramicidin, imipenem, iSoniazid, kanamycin, levofloxacin, general health and/or aging of one or more body systems. lincomycin, lineZolid, lomefloxacin, mafenide, meropenem, Active pharmaceutical ingredients include prodrugs, metabo methenamine, minocycline, moxifloxacin, mupirocin, nafcil US 2010/00151.84 A1 Jan. 21, 2010

lin, nalidixic acid, , nitrofurantoin, , 0061 Suitable bone disease agents include, but are not norfloxacin, ofloxacin, oxacillin, oxytetracycline, penicillin, limited to, alendronate, calcitonin, etidronate, ibandronate, piperacillin, polymyxin B. pyrazinamide, retapamulin, pamidronate, raloxifene, risedronate, tiludronate, and Zoledr rifabutin, rifampin, rifapentin, rifaximin, spectinomycin, Onate. streptomycin, Sulbactam, Sulfacetamide, Sulfadiazine, Sul 0062 Suitable botanicals include, but are not limited to, famethoxazole, Sulfanilamide, Sulfisoxazole, tellithromycin, agrimony, alfalfa, algae (red, brown, and green), aloe Vera, tetracycline, ticarcillin, tigecycline, tobramycin, trimethop anise, apple, ashwagandha, astragalus, barberry, barley, basil, rim, and Vancomycin. bilberry, blackberry, black cohosh, black currant, blackhaw, 0053 Suitable antidiabetic agents include, but are not lim black walnut, bloodroot, boneset, borage, boswellia, broom, ited to, acarbose, acetohexamide, chlorpropamide, exenatide, brussel sprouts, bugleweed, burdock, butcher's broom, cab glimepiride, glipizide, glyburide, insulin, levocarnitine, mef bage, calendula, camphor, cantaloupe, capsicum, caraway, formin, miglitol, nateglinide, pioglitaZone, pramlintide, repa cardamom, cascara Sagrada, catnip, cat's claw, cayenne, cel glinide, rosiglitaZone, Sitagliptin, thiazolidinedione, tolaza ery, chamomile, chaste berry, chicory, Chinese cucumber, mide, and tolbutamide. choke cherry, cinnamon, cleavers, cloves, cocoa, coltsfoot, 0054 Suitable antifungal agents include, but are not lim comfrey, coriander, cramp bark, cranberry, dandelion, devil's ited to, amphotericin B, anidulafungin, butenafine, butocona claw, dill, dong quai, echinacea, elder, eucalyptus, evening Zole, caspofungin, ciclopiroX, , clotrimazole, primrose, fennel, fenugreek, feverfew, flax, fig, garlic, gen econazole, fluconazole, flucytosine, griseofulvin, itracona tian, ginger, ginkgo, ginseng, goldenrod, goldenseal, gotu Zole, ketoconazole, metronidazole, micafungin, miconazole, kola, grape seed, grapefruit, guarana, guggul, hawthorn, naftifine, natamycin, nystatin, oxiconazole, posaconazole, hops, horehound, horse chestnut, horseradish, horsetail, hys Sertaconazole, Sulconazole, terbinafine, terconazole, tiocona sop, Iceland moss, ipecac, jasmine, jojoba, kava, kelp, kom Zole, and Voriconazole. bucha mushroom, lady's mantle, lavender, legumes, lemon, 0.055 Suitable antihistamines include, but are not limited lemon balm, licorice, lime, lovage, mango, marijuana, marsh to, acrivastine, antazoline, azelastine, bromazine, bromphe mallow, meadowsweet, milk thistle, mint, motherwort, mul niramine, carbinoxamine, cetirizine, chlorpheniramine, lein, mustard, myrrh, nettle, oak, oat bran, olive, onion, clemastine, cromolyn, cyproheptadine, desloratadine, dex orange, oregano, papaya, parsley, passionflower, pear, pep brompheniramine, dexchlorpheniramine, dimenhydrinate, permint, pineapple, plum, pomegranate, poppy, pumpkin diphenhydramine, doxylamine, emedastine, epinastine, etha seed, raspberry (red and black), red clover, red rice yeast, nolamine, fexofenadine, hydroxyzine, ketotifen, levocetiriz rose, rosemary, safflower, sage, St. John's wort, savory, saw ine, loratadine, meclizine, olopatadine, pheniramine, promet palmetto, Seneca root, Senna, Sesame, slippery elm, soapwort, hazine, and triprolidine. star anise, Strawberry, tea tree, thyme, tomato, turmeric, uva ursi, Valerian, Vervain, white willow, wild yam, wintergreen, 0056 Suitable anti-inflammatory agents include, but are witch hazel, yarrow, yellow dock, and the extracts of any of not limited to, amlexanox, celecoxib, clofazimine, the foregoing. diclofenac, diflunisal, dimethylsulfoxide, etodolac, fenopro fen, flurbiprofen, hydrocortisone, ibuprofen, indomethacin, 0063 Suitable cardiovascular agents include, but are not ketoprofen, ketorolac, mefenamic acid, meloxicam, nabume limited to, acebutolol, alliskiren, ambrisentan, amiodarone, tone, naproxen, nepafenac, oxaprozin, piroXicam, Sulindac, amlodipine, aprotinin, atenolol, atorvastatin, benazepril, betaxolol, bisoprolol, bosentan, bretylium, candesartan, cap tolimetin, and tromethamine. topril, carteolol, carvedilol, ciloStaZol, clofibrate, clonidine, 0057 Suitable antimicrobial agents include, but are not clopidogrel, diaZOxide, digoxin, diltiazem, dipyridamole, limited to, benzalkonium, benzethonium, , disopyramide, dobutamine, dolfetilide, doxazosin, enalapril, chloroxylenol, hexachlorophene, malathion, resorcinol, enalaprilat, epinephrine, eplerenone, epoprostenol, eprosar thimerosal, triclocarban, and . tan, eptifibatide, esmolol, ezetimibe, felodipine, fenofibrate, 0058 Suitable antiparasitic agents include, but are not fenoldopam, flecainide, fluvastatin, fosinopril, gemfibrozil, limited to, albendazole, atovaquone, chloroquine, diatrizoate, guanabenz, guanfacine, hydralazine, ibutilide, iloprost, eflornithine, hydroxychloroquine, iodoquinol, ivermectin, inamrinone, irbesartan, isoetharine, isoproterenol, isosor lindane, mebendazole, mefloquine, metronidazole, nitaZOX bide, isradipine, labetalol, levobunolol, lisinopril, losartan, anide, paromomycin, pentamidine, permethrin, piperonyl lovastatin, mecamylamine, methyclothiazide, methyldopa, butoxide, praziquantel, primaquine, proguanil, metoprolol, metyrosine, mexiletine, midodrine, milrinone, pyrimethamine, and tinidazole. minoxidil, moexipril, nadolol, naphazoline, nesiritide, nicar 0059 Suitable antivirals include, but are not limited to, dipine, nifedipine, nimodipine, nisoldipine, nitroglycerin, abacavir, acyclovir, adefovir, amantadine, amprenavir, ataza norepinephrine, olmesartan, penbutolol, pentoxifylline, per navir, cidofovir, darunavir, delavirdine, didanosine, indopril, phenoxybenzamine, phentolamine, pindolol, pra docosanol, efavirenz, emitricitabine, enfuvirtide, entecavir, Zosin, pravastatin, procainamide, propafenone, propranolol. famciclovir, fosamprenavir, foscarnet, ganciclovir, idoxuri quinapril, quinidine, ramipril, ranolazine, rescinnamine, dine, indinavir, lamivudine, lopinavir, maraviroc, nelfinavir, reserpine, rosuvastatin, sildenafil. Simvastatin, Sotalol, tad nevirapine, oseltamivir, penciclovir, raltegravir, ribavirin, alafil, telmisartan, tetrahydrozoline, ticlopidine, tirofiban, rimantadine, ritonavir, saquinavir, stavudine, telbivudine, trandolapril, trepostinil, Valsartan, Vardenafil. Verapamil, and tenofovir, thiabendazole, tipranavir, trifluridine, Valaciclovir, Xylometazoline. Valganciclovir, Zalcitabine, Zanamivir, and Zidovudine. 0064 Suitable dermatologic agents include, but are not 0060 Suitable biological and cellular agents include, but limited to, acitretin, adapalene, alitretinoin, allantoin, alpha are not limited to, antibodies, antigens, bacteria, cell frag hydroxy acid, anthralin, avobenzone, azelaic acid, bento ments, DNA, molds, phages, polynucleotides, polypeptides, quatam, benzoyl peroxide, calcipotriene, clobetasol, crotami RNA, stem cells, viruses, whole cells, and yeasts. ton, desonide, desoximetaSone, dioxybenzone, ecamsule, US 2010/00151.84 A1 Jan. 21, 2010

fluocinonide, flurandrenolide, halcinonide, hydroquinone, Sodium, Sulfur, , and the various salts thereof, including isotretinoin, meduinol, methoXSalen, methyl aminolevuli metal salts, halide salts, organic acid salts, alkoxide salts, nate, monobenzone, octinoxate, octocrylene, oxybenzone, carboxylate salts, ammonium salts, and the like. pimecrolimus, pramoxine, prednicarbate, sinecatechins, taZ 0070 Suitable neuromodulators include, but are not lim arotene, titanium dioxide, tretinoin, and Zinc oxide. ited to, acamprosate, acetylcholine, alprazolam, 0065 Suitable diuretics include, but are not limited to, ambenonium, amitriptyline, amoxapine, amphetamine, apo acetazolamide, amiloride, bendroflumethiazide, bumetanide, morphine, aripiprazole, armodafinil, atomoxetine, baclofen, chlorothiazide, chlorthalidone, ethacrynate, furosemide, hydrochlorothiazide, hydroflumethiazide, indapamide, met benZphetamine, benztropine, biperiden, bromocriptine, haZolamide, metolaZone, polythiazide, Spironolactone, bupropion, buspirone, butabarbital, cabergoline, caffeine, torsemide, and triamterene. carbamazepine, carbidopa, cevimeline, chlordiazepoxide, 0066 Suitable gastrointestinal agents include, but are not chlorpromazine, citalopram, clomipramine, clonazepam, limited to, alosetron, aluminum hydroxide, aprepitant, bal cloraZepate, clozapine, desipramine, dextromethorphan, Salazide, bisacodyl, bismuth Subsalicylate, cholestyramine, dexmethylphenidate, dextroamphetamine, diazepam, dieth cimetidine, colesevelam, colestipol, dicyclomine, difenoxin, ylpropion, divalproex, donepezil, doxepin, droperidol, dulox diphenoxylate, dronabinol, esomeprazole, famotidine, lactu etine, edrophonium, ergoloid, escitalopram, estaZolam, lose, lanSoprazole, loperamide, lubiprostone, mepenZolate, eSZopiclone, ethoSuximide, ethotoin, felbamate, flumazenil. mesalamine, methScopolamine, metoclopramide, misopros fluoxetine, fluiphenazine, flurazepam, fosphenytoin, gabapen tol, nizatadine, olsalazine, omeprazole, ondansetron, orlistat, tin, galantamine, haloperidol, imipramine, isocarboxazid, pantoprazole, rabeprazole, ranitidine, Scopolamine, simethi lamotrigine, levetiracetam, levodopa, lisdeXamfetamine, cone, sincalide, Sucralfate, SulfaSalazine, trimethobenza lithium, lorazepam, loxapine, maprotiline, memantine, mep mide, and ursodiol. robamate, methamphetamine, methSuximide, methylpheni 0067 Suitable hematologic and oncologic agents include, date, mirtazapine, modafinil, molindone, nalmefene, nalox but are not limited to, altretamine, amifostine, aminoglute one, naltrexone, nefazodone, nortriptyline, olanzapine, thimide, aminolevulinic acid, anagrelide, anastroZole, arga oxazepam, oXcarbazepine, paliperidone, paroxetine, pento troban, azacytidine, beXarotene, bicalutamide, bivalirudin, barbital, perphenazine, phendimetrazine, phenelzine, phe bortezomib, buSulfan, capecitabine, carboplatin, carmustine, nobarbital, phentermine, phenyloin, pimozide, pralidoxime, cetrorelix, chlorambucil, cisplatin, cladribine, clofarabine, pramipexole, pregabalin, primidone, prochlorperazine, pro cyclophosphamide, cyclosporine, cytarabine, dacarbazine, cyclidine, protriptyline, pyridostigmine, quazepam, quetiap dactinomycin, dalfopristin, dalteparin, dasatinib, daunorubi ine, ramelteon, rasagline, riluzole, risperidone, rivastigmine, cin, decitabine, deferasiroX, deferoxamine, desirudin, dexra ropinirole, rotigotine, secobarbital, selegiline, Sertraline, Zoxane, docetaxel, dolasetron, doxorubicin, enoxaparin, epi Sibutramine, tacrine, temazepam, thioridazine, thiothixene, rubicin, erlotinib, estramustine, etoposide, exemestane, tiagabine, tizanidine, topiramate, tranylcypromine, traZ floxuridine, fludarabine, fluorouracil, flutamide, fonda odone, triazolam, trifluoperazine, trihexyphenidyl, tri parinux, fulvestrant, gefitinib, gemcitabine, gemtuzumab, methadione, trimipramine, Valproate, Varenicline, Venlafax granisetron, heparin, hydroxyurea, idarubicin, ifosfamide, ine, Zaleplon, Ziprasidone, Zolpidem, and Zonisamide. imatinib, imiquimod, irinotecan, ixabepilone, lapatinib, lena (0071 Suitable nutraceuticals include, but are not limited lidomide, lepirudin, letrozole, leucoVorin, mechlorethamine, to, 5-hydroxytryptophan, acidophilus, alpha-linolenic acid, megestrol, melphalan, mercaptopurine, mesna, methotrexate, bee pollen, benecol, beta-carotene, beta glucan, brewer's mitomycin, mitotane, mitoxantrone, mycophenolate, nelara yeast, bromelain, carnitine, catalase, catechins, chalcones, bine, nilotinib, nilutamide, Oxaliplatin, paclitaxel, pal chlorophyll, cholestin, choline, chondroitin, coenzyme Qo. onosetron, pemetrexed, pentostatin, plicamycin, podofilox, creatine, dehydroepiandrosterone (DHEA), daidzein, dim procarbazine, protamine, quinupristin, Sirolimus, Sorafenib, ethyl sulfoxide (DMSO), docosahexanoic acid, eicosapen streptozotocin, Sunitinib, tacrolimus, tamoxifen, temozolo taenoic acid, flavonoids, genistein, glucomannan, glu mide, temsirolimus, teniposide, thalidomide, thioguanine, cosamine, glutamine, glycosides, hesperidin, isoflavones, thiotepa, tinzaparin, topotecan, toremifene, tranexamic acid, L-arginine, lactoferrin, lecithin, linoleic acid, lipoic acid, urokinase, valrubicin, vinblastine, Vincristine, Vinorelbine, malvin, melatonin, methylsulfonylmethane (MSM), narin Vorinostat, and warfarin. gin, palmitate, para-aminobenzoic acid, phenylalanine, phos 0068 Suitable hormones include, but are not limited to, phatidylserine, phytoestrogens, polyphenols, psyllium, chorionic gonadotropin, conivaptan, corticorelin, corticotro proanthocyanidins, pycnogenol, quercetin, resveratrol, rutin, pin, cosyntropin, danazol, desmopressin, desogestrel, doxer S-adenosylmethionine, Sesamol, shark cartilage, silymarin, calciferol, drospirenone, estradiol, estrogen, estrone, estropi soy protein, Spirulina, ubiquinol, Vinpocetine, and Xanthine. pate, ethynodiol, etonogestrel, follitropin, glucagon, 0072 Suitable obstetric and fertility agents include, but goserelin, histrelin, lanreotide, leuprolide, levonorgestrel, are not limited to, carboprost, choriogonadotropin, clo levothyroxine, liothyronine, lomustine, lutropin, mecaser mifene, dinoprostone, ganirelix, menotropin, methylergono min, medroxyprogesterone, mestranol, methimazole, nafare vine, mifepristone, and ritodrine. lin, norelgestromin, norethindrone, norgestimate, norgestrel, 0073 Suitable opthalmologic agents include, but are not octreotide, oxytocin, paricalcitol, pegvisomant, progester limited to, apraclonidine, atropine, bimatoprost, brimonidine, one, secretin, sermorelin, Somatotropin, teriparatide, thy brinzolamide, carbachol, cyclopentolate, diplivefrin, dorZola rotropin, triptorelin, and urofollitropin. mide, echothiophate, fluorescein, gatifloxacin, homatropine, 0069 Suitable minerals include, but are not limited to, hyaluronidase, hydroxyamphetamine, hydroxypropyl cellu boron, bromine, calcium, chloride, chromium, cobalt, copper, lose, latanoprost, lodoxamide, loteprednol, metipranolol. fluoride, iodine, iron, lithium, magnesium, manganese, naphazoline, pegaptanib, pemirolast, pilocarpine, rimex molybdenum, phosphorus, potassium, rubidium, selenium, olone, timolol, tropicamide, travoprost, and verteporfin. US 2010/00151.84 A1 Jan. 21, 2010

0074 Suitable proteins, enzymes and enzyme inhibitors may be complex. To add value. Such an excipient-only mod include, but are not limited to, adenosine, albumin, algluc ule may be useful for more than one final product; otherwise erase, aminocaproic acid, antigens, arginine, cilastatin, cla it would be simpler to use standard large-volume manufac Vulanate, cysteamine, cysteine, disulfuram, entacapone, turing or compounding techniques, for Some embodiments. fomepizole, glutamate, glutathione, glycine, glatiramer, imi Components of excipient modules may be selected for versa glucerase, metyrapone, miglustat, nitisinone, pegademase, tility in combination with the portfolio of API modules, and as propylthiouracil, protein fragments, Sacrosidase, taZobactam, the number and type of API modules changes, the portfolio of tolcapone, viruses. polynucleotides, excipient modules can be optimized. Some excipient modules 0075 Suitable respiratory agents include, but are not lim fall into these classes: fillers used in combination with solid ited to, acetylcysteine, albuterol, aminophylline, arformot dose API modules; and liquid carriers used in combination erol tartrate, benzonatate, beractant, budesonide, calfactant, with liquid dose API modules, which may contain one or ciclesonide, doxapram, dyphylline, formoterol, guaifenesin, more flavors, Sweeteners and other taste-masking agents, col ipratropium, levalbuterol, levonordefrin, menthol, metaprot ors, viscosity agents, preservatives, and antiseptics. erenol, methacholine, montelukast, nedocromil, oxtriphyl I0082 Ingredients of excipient modules include any suit line, oxymetazoline, phenylephrine, pirbuterol, poractant, able ingredients. Such ingredients include, but are not limited pseudoephedrine, salmeterol, terbutaline, theophylline, to, colorants, flavors, Sweeteners and other taste-masking tiotropium, Zafirlukast, and Zileuton. agents, fragrances, and other ingredients used to modify char 0076 Suitable rheumatologic agents include, but are not acteristics of the product, including solvents and Solutions, limited to, allopurinol, auranofin, azathioprine, colchicine, diluents, binders, fillers, disintegrants, lubricants, emulsifi leflunomide, penicillamine, probenecid, quinine, and Sulfin ers, carriers, Suspensions and Suspending agents, elixirs, pyrazone. acidifiers, alkalinizers and buffers, solubilizers, , 0.077 Suitable steroids include, but are not limited to, clarifying, gelling and/or thickening agents, viscosity alclometasone, amcinonide, beclomethasone, betametha enhancers, coatings, antioxidants, chelating agents, stabiliz Sone, clocortolone, cortisone, dexamethasone, diflorasone, ers, Sustained release agents, antiseptics, preservatives, and fludrocortisone, flunisolide, fluocinolone, fluorometholone, multifunction agents. fluoxymesterone, fluticasone, halobetasol, methylpredniso 0083 Suitable colorants include, but are not limited to, lone, methyltestosterone, mometasone, nandrolone, oxan dyes and inks approved for use in drugs and cosmetics drolone, oxymetholone, prednisolone, prednisone, testolac (D&C), dyes and inks approved for used in food, drugs and tone, testosterone, and triamcinolone. cosmetics (FD&C), branded dyes, inks, and coatings, other 0078 Suitable urological agents include, but are not lim dyes, and other inks. ited to, alfuZosin, alprostadil, bethanechol, darifenacin, I0084 Suitable D&C approved colorants include, but are dutasteride, finasteride, flavoxate, oxybutynin, pentosan not limited to, D&C Black #1, Blue #1, 2, and 6, Green #1, 4, polysulfate, propantheline, Solifenacin, tamsulosin, tera and 5, Orange #3, Red #3,4,5,6,7, 19, 21, 22, 27, 28, 30,33, Zosin, tiopronin, tolterodine, and trospium. 36, 39, and 40, Violet #2, and Yellow #5, 6, and 10, including 0079 Suitable vitamins include, but are not limited to, lakes. alpha-tocopherol (vitamin E), ascorbic acid (vitamin C), I0085 Suitable FD&C approved colorants include, but are biotin (vitamin B), cholecalciferol and calcitriol (vitamin not limited to, FD&C Blue #1, 2, 10, 40, Green #1 and 3, D), cyanocobalamin and hydroxocobalamin (vitamin B2), Orange #2, Red #1,2,3,4,7, 19, 27, 28, 30,33, and 40, Violet ergocalciferol (vitamin D), folic acid (vitamin Bo), inositol #1, and Yellow #1, 3, 5, 6, and 10, including lakes. (vitamin Bs), menaquinone (vitamin K2), mendione (vitamin 0.086 Suitable branded colorants include, but are not lim K), niacin and nicotinic acid (vitamin B), pantothenic acid ited to, BLUE TEK PRINT SE-6008 and SB-6029: and pantethine (vitamin Bs), phylloquinone (vitamin K). CHROMA-TERIC Deb-5037-Ore, T3000-We, and Yellow pyridoxine (vitamin B), retinol, retinoids, and carotenoids T3277-Ye: CHROMA-TONE PDDB-8906-W and PDDB (vitamin A), riboflavin (vitamin B), and thiamine (vitamin 8746-Or: CHROMACOTE T 2700GN, T 2716Y, and T B). 2956Y COATERIC YPA-6-7430 White and YPA-6-7089 0080 Suitable other agents include, but are not limited to, White; DIOLACK OOf32892 Yellow: DRI KLEAR: DRI alcohol, aminohippurate, cinacalcet, citrate, dextrose, dimer KLEAR 042; DRI KLEAR LV 609527; DRY FLO; DRY caprol, edetate, ferumoxides, ferumoxsil, fludeoxyglucose, CLEAR LV: DURO-TAK 80-1196, 87-2070, 87-2194, gadobenate, gadodiamide, gadopentetate, gadoteridol. 87-2287, 87-2296, 87-2888, 87-2979, and 280-2516; gadoversetamide, gallium, glycerin, icodextrin, indocyanine, FLEXOGRAPHIC Pink: PHARMACOAT 606: Red and iodipamide, iodixanol, iohexyl, iopamidol, iopromide, White COTOLENE-P; SPECTRABLEND Cs1-15764 iothalamate, ioVersol, ioxaglate, kaolin, lactate, lanolin, lan (Blue); SPECTRASPRAY Blue 50726; WHITE TEKPRINT thanum, mineral oil, pentetate, perflutren, porfimer, petrola SB-007p. tum, Samarium, sevelamer, strontium, Succimer, technetium, I0087 Additional branded colorants and coatings include, thallous chloride, and trientine. but are not limited to, OPACOAT Na2203, Na4108 Blue, Na4711 Lavender, NaT013 Clear; OPACODE A-10450 Modules not Containing an API Black, A-10509 Black, Ns-78-10013-N, Ns-78-17502 Gray, 0081 FIG.3 summarizes the process of developing a port Ns-78-17821, Ns-78-8000 Black, Ns-78-8001, Nsp-78 folio of and selecting the components in, modules not con 17734 Black, S-1-13001 Orange, S-1-15034-Fd Red, S-1- taining an API, for one embodiment of the present invention. 15038 Red, S-1-16507, S-1-1666 Red, S-1-1666-M Red, S-1- Whereas the key issues that govern the development of pre 1681 Red, S-1-17706 Black, S-1-17711 Black, S-1-17734 cursor modules that contain an API can be relatively straight Black, S-1-17749 Black, S-1-17762 Black, S-1-17797 Black, forward, the key issues that govern the development of pre S-1-18025 White, S-1-26514 Brown, S-1-3110 Green, S-1- cursor modules (especially liquids) that do not contain an API 3171 Green, S-1-4124 Blue, S-1-4157, S-1-4159 Black, S-1-

US 2010/00151.84 A1 Jan. 21, 2010

5-1727 Red, 5-2028 Yellow, 5-2042 Yellow, 5-2086 Yellow, 1-4700 Purple, 1-4710, 1-4739 Lavender, 1-4812 Lavender, 5-2312 Yellow, 5-2328 Orange, 5-2371 Orange, 5-2394 1-4845 Purple, 1-6275 Orange, 1-6300, 1-6312 Yellow, Orange, 5-2450 Orange, 5-2451 Orange, 5-2644 Beige, 1-6318 Yellow, 1-6320 Yellow, 1-6357 Yellow, 1-6370g Yel 5-2646 Beige, 5-3140 Green, 5-3171 Green, 5-3193 Green, low, 1-6378g Yellow, 1-6381 Yellow, 1-6382g Yellow, 5-3296 Green, 5-4129 Blue, 5-4270 Blue, 5-4287 Blue, 1-7000e White, 1-7002 White, 1-7003 White, 1-7003h White, 5-4295 Blue, 5-6233 Light Orange, 5-6301 Yellow, 5-6308, 1-7006 Clear, 1-7022 Off-White, 1-7027 White, 1-7040 5-7058 White, 5-7068 White, 5-7072 White, 5-7411 Purple, White, 1-7052 White, 1-7059 White, 1-7060 White, 1-7086 White, 1-7191 Brown, 1-7444g White, 1-7449 White, 1-7472 5-7524 Grey, 5-8050 Black, 5-9006 Brown, and 5-9020 Clear, 1-7507 Grey, 1-7552 Grey, 1-7700 White, 1-7706g Brown. White, 1-8325 Beige, 1-8343g Beige, 1-8345g Beige, 1-8608 0092. Also, OPADRY Yellow; OPADRY YPS-7-2127; Orange, 1-8619 Orange, 1-89193 Clear, 1-9011 Brown, OPADRYYS-1-003 White, 1-10010 Purple, 1-10291 Laven 1-9012 Brown, 1 r1418 Pink, 1 r-7006 Clear, 2-10657 Blue, der, 1-10523a Blue, 1-10525 Blue, 1-10533a, 1-10542a Blue, 2-19071a Clear, 2-19114a Clear, 22-16576 Brown, 22-18119 1-10547a Blue, 1-10563 Blue, 1-10613a Blue, 1-10618, White, 2-7013 Clear, 2-7063. White, 3-7011 Clear, 3-7031 1-10629, 1-10654a Blue, 1-10682 Blue, 1-10690a Blue, Clear,3-7413 Clear, 5-12575Yellow, 5-12576Yellow, 5-1260 1-10699 Blue, 1-10745 Blue, 1-10748a Light Blue, 1-10755 Pink, 5-1296 Pink, 5-17266 Tan, 5-18068 White, 5-18074 Blue, 1-10783a Blue, 1-1 1000 Pink, 1-11051 Green, 1-1 1060 White, 5-2085Yellow, 5-2370 Orange, 5-3116 Green, 5-4277 Green, 1-1107 Green, 1-1 1075a Green, 1-11 113 Green, Blue, 5-4278 Blue, 5-7017, 5-7042 Clear, 5-7068, and 5-7099 1-11171 Green, 1-11234 Green, 1-11305 Green, 1-11369 White. Green, 1-1246 Pink, 1-1252 Pink, 1-12524a Yellow, 1-12525aYellow, 1-12526aYellow, 1-12529 Yellow, 1-12541 0093. Also, OPAGLOS GS 2-0300 and 2-0310; OPAG Yellow, 1-1256-AYellow, 1-12573 Yellow, 1-12581 Yellow, LOSS 0750; OPALUXAS 1406 Pink, 1475 Pink, 1537 Pink, 1-1262 Pink, 1-12625 Yellow, 1-12702aYellow, 1-12732Yel 1589 Pink, 2006 Yellow, 2007 Yellow, 2052 Yellow, 2062 low, 1-1277 Pink, 1-12789 Yellow, 1-12826 Yellow, 1-1283 Yellow, 2086 Chartreuse, 2094, 2167 Yellow, 2236, 2269 Pink, 1-12844Yellow, 1-12847Yellow, 1-1298 Pink, 1-13013 Yellow, 2324 Orange, 2336 Orange, 2395 Peach, 2413, 2433 Peach, 1-13065a Orange, 1-13119 Orange, 1-13121 Yellow, Orange, 2490 Coral, 2498 Orange, 2553 Orange, 2612, 2613 1-13148a Orange, 1-13214 Orange, 1-13269 Orange, Tan, 2620-BTan, 2676 Salmon Jasper Red, 2754,2768,2787 1-13271 Orange, 1-13555 Orange, 1-13591a Orange, Butterscotch, 3140 Green, 3287, 3288 Green, 3308 Green, 1-13664a Orange, 1-13673a Orange, 1-13675a Orange, 3348-C Green, 3376, 3381, 3389 Green, 3391 Green, 3942 1-14012 Pink, 1-14129 Pink, 1-14130 Pink, 1-1418 Pink, Maroon, 4025, 4151 Blue, 4188 Blue, 4193 Blue, 4208-A 1-1441g, 1-1448g Pink, 1-14518a Pink, 1-14519a Pink, Blue, 4258 Blue, 4270 Blue, 4800 Lavender, 4854 Lavender, 1-14532 Pink, 1-1454 Pink, 1-14555a Pink, 1-14559 Pink, 4855 Purple,4891,5034 Red,5107,5162 Green, 5178 Green, 1-1456g Pink, 1-14587a Pink, 1-14593a Pink, 1-14595 Pink, 5203 Green, 5212 Green, 7000-B, 7000-PWhite, 7001, 7535 1-14608a, 1-14643a Pink, 1-14725 Pink, 1-14756a Pink, Gray, 8010-A Black, 8050-L Black, 9010 Brown, 9030 1-14779a Pink, 1-15050 Red, 1-1510 Pink, 1-1528 Pink, Brown, and 9050 Brown. 1-1543 Pink, 1-15585a Red, 1-16002 Maroon, 1-16518a (0094. Also, OPALUX Blue and Green: Opaque Blue 100, Brown, 1-17169a, 1-17180a Beige, 1-17181a Beige, Blue 147, Blue 605, Brown 85 Bf, Green 1664, Green 97, 1-17192a, 1-17209 Beige, 1-17220, 1-17222a Tan, 1-17235a Green/Flesh, Maroon 6 Dar, Pink 0439, White 001, White Peach, 1-1724 Red, 1-17274a Beige, 1-17277a Beige, 002, White 535, White 536, White 538, and White 8. 1-17307a Butterscotch, 1-17505a Gray, 1-17506a Gray, 0.095 Also, OPASPRAY3-1700,3-1810,3-1820, 3-1830, 1-1751g Red, 1-1755 Gray, 1-18005 White, 1-18022 White, Im-176, K-1-1230 Pink, K-1-1243, K-1-1254, K-1-1279, 1-18027 White, 1-18027a White, 1-18028 White, 1-18097a K-1-1289 Pink, K-1-14016 Pink, K-1-1413 Pink, K-1-1414 White, 1-1811 Red, 1-18111 White, 1-18130a White, 1-1814 Pink, K-1-1432, K-1-1437, K-1-1455 Pink, K-1-1526 Pink, Red, 1-18177a White, 1-18202a White, 1-18229 White, K-1-1563 Pink, K-1-1573 Lavender, K-1-1574, K-1-1584, 1-1846 Red, 1-1847 Red, 1-1891 Red, 1-19025-A Clear, K-1-1719 Red, K-1-2004 Yellow, K-1-2013 Yellow, 1-2007 Yellow, 1-2013 Yellow, 1-2053 Yellow, 1-2063 Yel K-1-2043 Yellow, K-1-2182 Yellow, K-1-2186 Yellow, K-1- low, 1-2074 Yellow, 1-2083 Yellow, 1-2115 Yellow, 1-2122 2216-A Yellow, K-1-2227 Yellow, K-1-2228 Yellow, K-1- Yellow, 1-2134 Yellow, 1-2135 Yellow, 1-2136 Yellow, 2239, K-1-2240 Yellow, K-1-2256Yellow, K-1-2275 Yellow, 1-2141 Yellow, 1-2152 Yellow, 1-2167 Yellow, 1-218.1 Yel K-1-2300 Peach, K-1-2301 Peach, K-1-2303 Orange, K-1- low, 1-2184 Gold, 1-2186 Yellow, 1-2192 Yellow, 1-2305 2304 Orange, K-1-2314 Orange, K-1-2327 Orange, Orange, 1-2308 Dark Orange, 1-2344 Yellow, 1-2383 K-1-2330 Orange, K-1-2335 Orange, K-1-2406 Orange, Orange, 1-2398 Orange, 1-2449 Orange, 1-2455 Red, K-1-2410 Orange, K-1-2417 Orange, K-1-2430, K-1-2441 1-2465, 1-2487 Orange, 1-2522 Orange, 1-2526 Orange, Orange, K-1-2471 Orange, K-1-2473, K-1-2492, K-1-2531, 1-2527 Orange, 1-2534, 1-2546 Orange, 1-2548 Orange, K-1-2533 Orange, K-1-2554, K-1-2568 Orange, K-1-2570 1-2549 Orange, 1-2558 Orange, 1-2563 Orange, 1-2564, Orange, K-1-2588 Orange, K-1-2614 Beige, K-1-2621 1-2578 Orange, 1-2596 Orange, 1-2604 Beige, 1-2612 Beige, Brown, K-1-2626 Orange, K-1-2656 Beige, K-1-2670 Tan, 1-2619, 1-2621 Rust, 1-2623 Brown, 12630 Yellow, 1-2635 K-1-2674 Beige, K-1-2685, K-1-2711, K-1-2723 Butter Tan, 1-2660 Salmon, 1-2665 Beige, 1-2669 Rust, 1-2671 scotch, K-1-2837, K-1-3000, K-1-3142 Green, K-1-3144 Beige, 1-3105 Green, 1-3130 Green, 1-3134 Green, 1-3146 Green, K-1-3147, K-1-3148 Green, K-1-3156, K-1-3173 Green, 1-3147, 1-3166 Green, 1-3256 Green, 1-3288 Green, Green, K-1-3178 Green, K-1-3197 Green, K-1-3202 Green, 1-4014 Blue, 1-4018 Blue, 1-4112 Blue, 1-4137 Blue, K-1-3209 Green, K-1-3220 Green, K-1-3227, K-1-3300-A 1-4215, 1-4216, 1-4221 Blue, 1-4228 Blue, 1-4229 Blue, Green, K-1-3300-C Green, K-1-4108 Blue, K-1-4119, K-1- 1-4234 Blue, 1-4235 Blue, 1-4236 Blue, 1-4240 Blue, 1-4241 4122 Blue, K-1-4136 Blue, K-1-4205 Blue, K-1-4210-A, Blue, 1-4245 Blue, 1-4249 Blue, 1-4251 Blue, 1-4254, K-1-4213 Blue, K-1-4214, K-1-4227, K-1-4234 Blue, K-1- 1-4255, 1-4256 Blue, 1-4282 Blue, 1-4298 Blue, 14644 Pink, 4235 Blue, K-1-4728, K-1-4731 Purple, K-1-4743 Lavender, US 2010/00151.84 A1 Jan. 21, 2010

K-1-4786, K-1-5024 Red, K-1-7000 White, K-1-70008 46971; Creme de Menthe 14677; Creme de Vanilla 28156: White, K-1-7000b, K-1-7076, K-1-9027 Brown, K-1-9039-L Curacao 50.397A; and Custard 52.940/A FIR. Brown, K-1-9060 Red, K-1-9080 Brown, K-1-9112 Brown, 0099. Also, DF-119, DF-1530, and E-472: Enhancer L-2113, L-3305 Green, L-3306 Green, L-7000 White, M-1- F-5397A and F-9843; FIG. 827118: Fritzsche 21028-D, 2042, M-1-3459 B Orange, M-1-4395b Blue, M-1-7111-B, 46215, 73959, 75021, and 78087; Fruit 01-10428 and M-1-711b White, M-1-7120 White, M-1-8429 Yellow, and 84.6422: Fruit Gum 912; Fruit Mint 75588; Fruit Punch #716, Wd-1270 Pink; OPATINT Ad-25000 Red, Dd-13009 Orange, #28140, and 14761 FM; Grape 59.145/APO5.51, 59.266/ Dd-14000 Pink, Dd-1800 White, and Dd-18000 White. APO5.51, 6175, 054158,486939, 501040A, 13403873, IFF 0096 Suitable other dyes include, but are not limited to, 13549478, PFC 8439, PFC-9711, and PFC-9924: Guarana Beige P-1437; Black LB-260, 442, 636, 1171, and 9972: FMC-15417; IFF FP 69 F: Kiwi S-718; Lemon 812 and Black Oxide: Blue LB-332, 781, and 1245; Blue Lakolene; FMC-10471; Lemon Mint 862.547; Lemon Mint Fritzsche Brown LB-292, 464, 1685, 1792, and 56069: Burnt Umber; 54369; Lemon Spray V3938-1 N1; Mandarin 15228-71; Caramel 105; Caramel Acid Proof 100; Carmine 09349; Cas Maque Tree 377(BUSH); Mask RBT-NV-7759; Masking ing 27-75; Emerald Green LB-9207; Ferric Oxide Brown, 35321; Menthol Mint PFC-9926; Mint 287,51296 TP0551, Green, Orange, Pink, Red, Red-Brown, and Yellow; Gray and SN027513; Mixed Fruit PFC-9970; and NNS DZ-03226. #2982: Green 70363; Green LB-265,279,333,482,555, 603, 0100 Also, Orange #7679, 9/79J839, 57.458/AP05.51, 820, 883, 1174, 1236, 1441, 1594, 1616, 1644, 3323, and 739K (PB82), 13334, 74016-71,249792, 607217, G-10431, 9583; Green PB-1543 and 1766; Green PMS-579; Green P-5614, and PFW-73.0016U; Orange Banana WL-18093: PR-1333 and 1339; Lavender LB-1356 and 1603; Mint Orange Pineapple FV-43: Peach 10457, 302789, and Green; Ochre 3506; Orange 54172: Orange LB-452, 715, 13503584; Peach Mint Fritzsche 106109; Peach Pineapple 1387, 1439, and 3810: Peach LB-1576; Pink; Purple LB-562, FMC 14258: Peppermint 104, 517, 894. 143, K373, PFC 588, 639, 694, and 1902: Red LB-6053-R and 9570; Red 9927, and WL-6167; Peppermint Stick FMC 16170; Pine PB-1595; Salmon LB-1668; Swedish Orange #2191; Tan apple 182661, N-2566, and N-2766; Pineapple-Coconut, Pri PB-1388; Tetrarome Orange: Turquoise LB-1430; White mary Taste Modifier #29275; Punch 610962U and WL-7126; TC-1032: Wild Cherry 7598; Yellow LB-104, 111, 1577, Raspberry 954, 954K (BK77), 998, 1840, 8456, 21028D, 1637, 1769, and 9706; Yellow PB-1345 and 1381; Yellow 28106, 50776, 65934, 262085, A11693, D9599, DY-04447, WD-2014; Yellow #70362; and Yellow Ochre. F-1784, F-1840, F-6887-S, and PFC-8407; and Root Beer 0097 Suitable other inks include, but are not limited to, 180339. Black 2271, A-10464, A-10527, FGE-1386, GG-606, S-1- 10101 Also, Strawberry 052311 AP0551, 133.5655, 17.36. 8100-Hv, SW-9007, SW-9008, SW-9009, and SW-9010; 8509, 17C56217, 52.311AP5210(FD&D), 52312/AP, 5951, Blue and Yellow Imprint GG-823: Blue Black A-10463, and 9843, 14953, 55058, 523121A, DY-04359, F-5665, F-5930 A-9371; Blue S-1-10551 and S-1-4118: Dark Yellow and A, FN-13819, PFC-9626, and WL-16650; Strawberry Yellow Imprint GG-824; Edible Black, Blue, Brown, Gray, Guarana 586.997/APO5.51; Sweet 24052 and 604978: Sweet Orange, Pink, Red, Red A-8032, and White; Fine Black Tone 28837 and AM 918.005; Sweetness Enhancer 5401 B; 2202c and 2212; Green A-10454 and A-10629; Orange and Tangerine Fritzsche 51465; TM 313298; TPF 135 and TPF Yellow Imprint GG-822; Pink Imprinting SB-1003: Red 5-1- 143: Tropical Blend FV-50; Tropical Fruit Punch 1591 and 9034 and A-8032; Red and Aqua Imprinting GG-827; Red N&A 50432: Tutti Frutti 0002028, 24093FM, 51.880/AP05. and Caramel Imprinting Gg-825; Red Imprinting Gg-826; 51, P-5400, and WL-18481; Vanilla 323453,33869, 501441 S-1-7085; Thinner; and White 21-K, A-8154, S-1-7075, and AP2004, F-6257, P-1160, PFC-8541, and PFC-9772: Wild SB-0007p. Cherry 29653, 695047U, K-321, NV-101-1489, PFC-14783, 0098 Suitable flavors, sweeteners, and taste-masking and WL-1093: Wintergreen PFC-8421, Yellow Plum Lemon agents include, but are not limited to, Anise 29653: Apple 39K 020, High Fructose Corn Syrup; and Flavors #18317, Watermelon PFC 9887; Apricot 23067 and 24829; Apricot 57000 IU, 57820/A, 89-186, and 89-259, and other sweeten Peach: Banana 15223,501013 AP0551, 71507,74546, FMC ers and taste-masking agents. 23406, and SA84; BBA-47769; Berry Citrus Blend 8409, 0102 Suitable branded flavors include, but are not limited 9621, and 9756: Bitter Mask 9885; Bitterness Modifier to, AROMALOK 182608 and 262453; Banana 15555, 36734, and 367343; Black Cherry 501027 AP0551; DURAROME860.095 TD09.91; C&K Mixed Fruit A13688; Blood Orange 51.226T and SA: Bubble Gum 15864, 175303, Cheri Beri PCD-5580, PFC-8573, PFC-8580, and PFC-8573; 3266P, and MC-4938: Buttermint 24020; Butterscotch Cherry DURAROME 860.097 TD10.91; Cherry E.P. Modi 61005-U and F-1785; Candied Sugar 510155U; Cherry fied 151; Cherry FONA 825.662; Cherry H&R PHARMA 57.679/A, 213,349,594 S.D., 825.476WC,842, 1566,3321, 004: Cherry WIXON 3566; FELTON 6-R-9; FLORA 8513, 11539, 11929, 104613, 107026, 181612, 231494, SYNTH; Fruit Tak 20008; Grape FIRMENICH 587.444 and 338614, 500910U, 590271A, 5983.84, A-22872, DP300.684, 597.303/C; Grape GIVAUDAN 433 160; Grape MANHE EP-3699, F-232, FI-8568, FMC 22872, FMC 8513, IFF IMER 522463; Grape MICRON ZD-3876; Grape Nector 13530912, L-1233, N-2755, NV-1489, PFC-9768, R-6556, PFC-8599; HAVERSTROOZD 49284; Lemon GIVAUDAN WL-1093, WL-18022, and WL-4658; Cherry Berry F-1194: 74940-74; MAGNASWEET 100, 110, 135, 180, and 185: Cherry Blend 770; Cherry Burgundy 11650; Cherry Cream MCP Lemon DURAMONE 4409A: MCP Lime DURA 14850; Cherry Maraschino S-3531, Cherry Mint 5073A: MONE 6419; Menthol VERALOCK; Orange GIVAUDAN Cherry Pistachio PFC-8450; Cherry Vanilla Compound 74388-74; Orange WONF 608352: Orbit Serene 20340; Pep A77487; Cherry-Anise PFC-9758; Chloroform 103589; permint SEELOCK 34907; PERLAROM Strawberry: Phar Chocolate P727; Coconut 41 and F-3893: Coconut Toasted maceutical 182608: PHARMASWEET 10772900; 1323PG: Cola FMC 15740; Cotton Candy 30-92-0011 and PLUSWEET; PROSWEET 604, 694, and K; Raspberry F-9967; Cough Syrup 819, 110257, and 134681; Cream AROME PFC-9908; Raspberry POLAK 5000064; EP-17688; Cream Soda; Creamy Vanilla 16345; Creme Refrachessment FD-8027D; RHODIA PHARMACEUTI US 2010/00151.84 A1 Jan. 21, 2010

CAL #RF 451; Strawberry MICROSEAL: Strawberry TRU hydroxide, lactate, phosphate, pyrophosphate, Salicylate, SIL WINDSOR 237303; TETRAROME: Tutti Frutti PER Stearate, Sulfate, Sulfate dihydrate, and Sulfate hemihydrate, MASEAL 77919-31; Vanilla BECK C7984; VERALOCK and other calcium compounds. Bubble Gum; and Wild Cherry GIVAUDAN F-1813. 0111. Also, caldiamide sodium; calteridol calcium; can 0103 Suitable fragrances include, but are not limited to, delilla wax, canola oil; caprylic triglyceride; capsicum oleo Essence Bouquet 9200, Fritzbro Orange, Lemon, and resin; captan; and caramel. Orange; Fragrance 3949-5, 520a, 6.007, 91-122,9128-Y. 93498g, Balsam Pine #5124, Bouquet 10328, CHEMOD (O112 Also, carbomer 934, 934p, 940, 941, 974, 974p, ERM 6401-B and 6411, Cream #73457, CS-28197, Felton 980, 981, and 1342; carbon; carbon black; carbon dioxide: 066m, FIRMENICH 47373, GIVAUDAN Ess 9090/Ic, carboxy vinyl copolymer; carboxymethyl starch; carboxym H-6540, Herbal 10396, Ni-1085, POF1-147, Pa52805, PERA ethylamylopectin Sodium; carboxymethylcellulose; carboxy DERM D, Rbd-9819, SHAW Mudge U-7776, Tf 044078, polymethylene; cardamom, carmine; carmine 50: carnauba UNGERER Honeysuckle K2771, and UNGERER N5195; wax, carrageenan; cassia oil; castor oil; cedar leaf oil; cel and Perfume 25677, Bouquet, E-1991, Gd5604, TANA90/42 lacefate; cellulose; cellulose acetate; cellulose acetate O-320s Scba, and W-1952-1. and ca-398-10; cellulose microcrystalline; cellulosic poly 0104 Suitable other excipients include, but are not limited mers; cerasynt-se; and ceresin. to, 1,1,1-trichloroethane; 1,1,2,2-tetrafluoroethane; 1,2,6- 0113 Also, ceteareth-12, 15, and 30; cetearyl alcohol and hexanetriol: 1,2-dimyristoyl-sn-glycero-3-(phospho-S-(1- octanoate; ceteth-2, 10, 20 and 23; cetrimonium chloride; glycerol)); 1,2-dioleoyl-sn-glycero-3-phosphocholine; 1.2- cetyl alcohol, esters, and palmitate; ; dipalmitoyl-sn-glycero-3-(phospho-rac-(1-glycerol)); 1.2- chartreus colored spheres; chemoderm 6401b; cherry; chlo distearoyl-sn-glycero-3-(phospho-rac-(1-glycerol)); 1,3- robutanol; chlorobutanol hemihydrate; chlorocresol; chloro dimethylol-5,5-dimethyl-hydantoin: form; chloroxylenol; cholesterol: choleth; cinnamaldehyde: 1-aminocyclohexanecarboxylic acid, c-1 1; 1-methyl-2-pyr cinnamon; citric acid; citric acid monohydrate; clove oil; rolidinone: 1-o-tolylbiguanide, 2-amino-2-methyl-1-pro cocamide diethanolamine and ether Sulfate; cocamine oxide; panol; 2-ethylhexyl salicylate; and 2-maptholene Sulfonate coco betaine; cocoa bean and butter, cocoglycerides; Sodium salt. cocomonoethanolamide; coconut oil; coffee; collagen; com 0105. Also, acacia; acesulfame potassium; acetic acid; pressible Sugar, copovidone; coriander oil; corn glycerides; acetic anhydride; acetone; acetone sodium bisulfite: corn oil; corn oil peg-6 esters; corn syrup; cottonseed oil; acetophenone; acetylated monoglycerides; acetylcysteine; cream base; creatine; creatinine; cresol; croScarmellose acetyltributyl citrate; acetyltryptophan; acrylates copolymer; sodium; crospovidone; crystal gum; cupric sulfate; cutina; acrylic acid; activated charcoal; adipic acid: AEROTEX resin cyclamic acid; cyclomethicone; cysteine; and cysteine hydro 3730; agar, air; alanine; albumin; alcohol; alfadex: alginic chloride. acid; alkyl ammonium Sulfonic acid betaine; alkyl aryl 0114. Also, dehydroacetic acid; dehymulse: denatonium Sodium Sulfonate; allantoin; almond oil; alpha-terpineol; benzoate; deoxycholic acid; dextran; dextran 40; dextrates; alpha-tocopherol; and althea. dextrin; dextrose; diacetylated monoglycerides; diatoma 0106 Also, aluminum acetate, chlorhydroxy allantoinate, ceous earth; diatrizoic acid; diazolidinylurea; dibutyl phtha diacetate, hydroxide monostearate, oxide, polyester, potas late: dibutyl sebacate; dichlorobenzyl alcohol; dichlorodif sium sulfate, silicate, silicate pentahydrate, starch octenyl luoromethane; dichlorofluoromethane; Succinate, Stearate, and Sulfate, and other aluminum com dichlorotetrafluoroethane; diethanolamine; diethyl phthalate pounds. and sebacate; diethylene glycol monoethyl ether, diglycol 01.07 Also, ALZAMER-39 and 50; AMBERLITE; Stearate, dihydroxyaluminum glycinate, dihydroxyalumi AMERCHOL c and cab; ammonia; and ammonio methacry num sodium carbonate; diisopropanolamine; diisopropyladi late copolymer. pate; diisopropyl dimerate; and diisopropylbenzothiazyl-2- 0108. Also, ammonium acetate, calcium alginate, chlo Sulfenamide. ride, glycyrrhizate, hydroxide, lauryl Sulfate, nonoxynol 4 0115 Also, dimethicone 350, 360, copolyol, and mdx4 Sulfate, phosphate, and Sulfate, and other ammonium com 4210; dimethyl dioctadecylammonium bentonite, isosorbide, pounds. phthalate, siloxane, and Sulfoxide; dimyristoyl lecithin; dio 0109 Also, ammonyx; amphoteric-2; amphoteric-9; amyl ctylphthalate; dipropylene glycol, disodium cocoamphodiac acetate; anethole; anidrisorb 85/70; anise; anoxid sbn; anti etate, edisylate, laureth SulfoSuccinate, lauryl SulfoSuccinate, foam; antipyrine, apricotkernel oil peg-6 esters; aquacel 126; and Sulfosalicylate; disofenin; divinylbenzene Styrene aquacoat, aquaphor, arginine; arlacel, arlatone 289; ascorbic copolymer, docosanol; docusate sodium; and dusting pow acid; ascorbyl palmitate; aspartame; aspartic acid; attapulg der. ite: balsam; barium sulfate; b-cyclodextrin sulfobutyl ether 0116. Also, edamine: edetate calcium disodium, diso sodium; beeswax; beheneth-10; bentonite; benzaldehyde; dium, and Sodium, egg yolk phosphatides; eiderdown soap: ; benzenesulfonic acid solution; ben entSulfon; epilactose; erythorbic acid; ethanolamine hydro Zethonium chloride; benzododecinium bromide; benzoic chloride; ether, ethyl acetate, hexanediol, maltol, oleate, and acid; benzoin; benzyl alcohol, benzoate, and chloride; beta vanillin; ethylcellulose; ethylene; ethylene glycol; ethylene dex; beta-naphthol; betose; bibapcitide; bismuth subcarbon glycol monoethyl ether, ethylene vinyl acetate copolymer; ate and Subgallate; boric acid; brocrinat, butane; butyl alco ethylenediamine dihydrochloride; ethylene-propylene hol, ester, and Stearate; butylated hydroxyanisole and copolymer, ethylparaben; eucalyptol; and eucalyptus oil. hydroxytoluene; butylene glycol; butylparaben; c20-40 0117. Also, EUDRAGIT E 100, L 100, L 100-55, L30 D, pareth-24; and caffeine. 130D-55, NE 30 D, NE 40D, RL100, RL 12.5, RL30 D, RS 0110. Also, calcium acetate, alginate, ascorbate, carbon 100, RS 12.5, RS 30 D, and S 100, and other EUDRAGIT ate, carrageenan, chloride, citrate, cyclamate, gluceptate, products. US 2010/00151.84 A1 Jan. 21, 2010

0118. Also, eugenol; exametazime; fampiridine; fatty acid methylisothiazolinone; methylphenidate; microcrystalline esters, glycerides and pentaerythriol ester, fatty acids; fatty wax; mineral oil; mineral spirits; mistron spray talc; alcohol citrate; fatty alcohols; ferric chloride and oxide; fer monoglycerides; monosodium citrate; montan wax, mullein rosoferric oxide; ferrous fumarate and oxide: FIRMENICH leaf multisterol extract; muscatel wine, myristic acid; myri 51.226/t; florasynth; flour; fluorescein; fluorochlorohydro styl alcohol and lactate; and myristyl-gamma-picolinium carbons; formaldehyde; fructose; fumaric acid; and fused chloride. Sodium ash. I0126. Also, n,n-bis(2-hydroxyethyl)stearamide: n,n-dim 0119) Also gadolinium oxide; galactose; gamma-cyclo ethyl lauramine oxide; n,n-dimethylacetamide; n-3-chloroal dextrin; gelatin; gelatin 200 bloom; gellan gum; gelucire lyl-methenamine chloride; naphtha; n-decyl-methyl sulfox 33/01; gelva 737; gentisic acid; gentisic acid ethanolamide: ide; neutral oil; niacinamide; nioxime; nipasept, nipastat; ginger fluidextract; gluceptate Sodium; gluceptate sodium nitric acid; nitrogen; n-lauroylsarcosine; nonoxynol iodine; dihydrate; gluconolactone; glucose: glucuronic acid; nonoxynol-9 or 15; non-pareil seeds; norflurane; n-propyl glutamic acid hydrochloride; glutathione; gluten; glycerin; orthosilicate; and nutmeg oil. and glycerol ester of hydrogenated rosin. I0127. Also oatmeal; octadecene-1/maleic acid copoly 0120 Also, glyceryl behenate, caprylate, citrate, distear mer, octanoic acid; octoxynol-1, 9, and 40; octyl hydroxys ate, isostearate, laurate, oleate, palmitate, palmitostearate, tearate; octyldodecanol; octylphenol polymethylene; oil ricinoleate, and Stearate; glycine; glycocholic acid; glycol cream soda, oleic acid; oleth-2, 5, 10, and 20; oleyl alcohol distearate and Stearate; glycyrrhizic acid; green starch blend; and oleate; olive oil; orange juice, orange oil; orange peel guanidine hydrochloride; guar gum, gum rosin; and gum. extract; orvusk liquid; oxidronate Sodium; and oxyquinoline. 0121. Also HERBACOL: hetastarch; hexane: hexylene I0128. Also palm kernel oil; palm oil; palmitamine oxide: glycol; histidine: hyaluronate sodium; hydrocarbon; hydro palmitic acid; parabens; paraffin, peanut oil; pectin; PEG chloric acid; hydrocortisone; hydrogel polymer, hydrogen 6-32 stearate, sorbitan isostearate, vegetable oil, -22 methyl peroxide; hydrogenated palm; hydroxyethyl cellulose and ether, -25 propylene glycol Stearate, -40 sorbitan diisoStear cellulose 2501; hydroxyethylpiperazine ethane sulfonic acid; ate, -45/dodecyl glycol copolymer, and -8 caprylic/capric hydroxymethyl cellulose; hydroxyoctacosanyl hydroxy Stear glycerides; peglicol-5-oleate; pegoXol 7 Stearate; pentadeca ate; hydroxypropyl cellulose and celluloself hydroxypropyl lactone; pentaerythritol cocoate; pentasodium triphosphate: ethylcellulose 2501; hydroxypropyl methylcellulose 100, pentetate calcium trisodium; pentetate pentasodium; pentetic 603, 606, 2208, 2906, 2910, 4000, acetate succinate, e5, and acid; peppermint; perflutren; petrolatum; petroleum distil phthalate; hydroxypropyl-b-cyclodextrin; and hystrene. lates: PHARMABURST b1: PHARMABURSTb2; pharma 0122. Also illicium anisatum; imidurea; insulin beef and ceutical glaze: PHARMATOSE dclii; phenethyl alcohol: pork; invert Sugar, iodine; iodoxamic acid; iofetamine hydro phenol; phenonip; phenoxyethanol; phenylalanine:phenylm chloride; irish moss extract; iron Subcarbonate; isobutane; ercuric acetate and nitrate; phosphatidylglycerol; phospho isobutyl alcohol; isoceteth-20; isoleucine; isomalt, isoocty lipid; phospholipon 90g, phosphoric acid; pine needle oil; lacrylate; isopropyl alcohol, isostearate, myristate, palmitate, pineapple; piperazine; piperazine hexahydrate; placebo. and Stearate; isostearic acid; and isostearyl alcohol. PLASTIBASE-50w; polacrilin: polish wax 7625 p 100; pol 0123. Also jelene; kaolin; karayagum, kathon cg, kathon ishing solution im-182; poloxamer 124, 181, 182, 188, 237, cgii, kola nut extract; lac resin; lactate; lactic acid; lactitol 331, and 407: polybutene; polycarbophil; polydextrose; poly monohydrate; lactobionic acid; lactoferrin; lactose; lactose dextrose k, polyester, polyester fluorocarbon diacrylate, monohydrate; landalgene; landalgine p; laneth; lanolin; lano polyamine copolymer, and rayon; and polyethylene. lin alcohols; lanolin cholesterols; lanolin nonionic deriva I0129. Also polyethylene glycol 200, 300, 300-1600, 400, tives; lauralkonium chloride; lauramine oxide; laurdimonium 540, 600, 800, 900, 1000, 1450, 1500, 1540, 3350, 3500, hydrolyzed animal collagen; laureth Sulfate; laureth-4 and 23; 4000, 4500, 6000, 7000k, 8000, and 20000, and other poly lauric diethanolamide and myristic diethanolamide; lauroyl ethylene products. polyoxylglycerides; lauryl Sulfate; lavender, lecithin; lemon 0.130. Also, polyethylene oxide:polyethylene oxide 200k, oil; leucine; levomenthol; lidofenin; light mineral oil; lime 7000k, t, and terephthalates; polygalacturonic acid; polygla oil; limonene; lipocol sc-15; lithium hydroxide monohydrate; ctin; polyglyceryl-10 oleate and tetralinoleate; polyglyc locust bean gum, lubritab; and lysine. eryl-3 oleate; polyglyceryl-4 oleate; polyhydroxyethyl meth 0124. Also, magnesium acetate, aluminum silicate, alumi acrylate:polyisobutylene; polyisobutylene 35,000 and 1,200, num silicate hydrate, aspartate, carbonate, chloride, hydrox 000; polylactide; polyols; polyoxyethylene alcohols: ide, nitrate, oxide, phosphate, silicate, Stearate, Sulfate, tar polyoxyethylene fatty acid esters; and polyoxyethylene pro trate, and trisilicate, and other magnesium compounds. pylene. 0125. Also, maleic acid; malic acid; maltitol; maltodex I0131. Also, polyoxyl 2, 8, 20, 40, 50, 100 and 400 stearate, trin; maltol; maltose; mannitol; mannitol 60,2080, and m300; 4 dilaurate, 6 isostearate, 6 and 8 laurate, 6 and 32 palmito mannose; maprofix, mebrofenin; medronate disodium; stearate, 15 cocamine, 20 cetostearyl ether, 35, 40 and 60 medronic acid; meglumine; melojel; menthol; metaphospho castor oil, 100 glyceryl Stearate, 150 distearate, and 75 lano ric acid; methacrylic acid copolymer, methanesulfonic acid; lin; polyoxyl distearate, glyceryl Stearate, lanolin, palmitate, methionine; methoxypolyoxyethylene glycol 350; methyl and Stearate. acrylate-methyl methacrylate; methyl alcohol, boronic acid, 0.132. Also, polyoxylethylene isononylphenyl ester; chloride, and ethyl ketone; methyl gluceth-10, 20, and 120 polypropylene; polypropylene glycol; polyduaternium-1, 7. dioleate; methylglucose sesquistearate, hydroxyethyl cellu and 10; polysaccharides; polysaccharides Soy; polysiloxane: lose, laurate, paraben, salicylate, and Stearate; methylated polysorbate 20, 40, 60, 65 and 80; polyurethane; polyvinyl spirits; methylcellulose 400, 1500 and 4000; methylchlor acetate, acetate phthalate, alcohol, acetal, pyridine, and pyr oisothiazolinone; methylene blue; methylene chloride; rolidone ethylcellulose; poppy seed oil; and potash. US 2010/00151.84 A1 Jan. 21, 2010

0.133 Also, potassium acetate, bicarbonate, bisulfite, ceth-10; triethyl citrate; trifluoroacetic acid; triglycerides: bitartrate, carbonate, chloride, citrate, hydroxide, met trihydroxy Stearin; trilaneth-4 phosphate; trilaureth-4 phos abisulfite, metaphosphate, Soap, and Sorbate, and other potas phate; trimyristin; triolein; trisodium citrate dihydrate; triso sium compounds. dium hedta; tristearin; triton 720; trolamine; tromethamine; 0134. Also, povidone acrylate copolymer, hydrogel, k17, tryptophan; tyloxapol; and tyrosine. k25, k26/28, k29-32, k30, k90, and k90f povidone/eicosene copolymer; PPG-12/smdi copolymer, -15 stearyl ether, -20 0.139. Also, UNION 76 AMSCO-res 6038; urea: valine: methyl glucose ether distearate, and -26 oleate; primajel; Vanillin, vegetable oil and shortening; Velvetine black pow proline; promalgen type D and G., propane; propellanta-46; der; versetamide; vinyl acetate; Viscarin; Viscose/cotton; Vita mine; wax, wecobeefs; wheat flour, white ceresin wax, Xan propenyl guaethol; propyl gallate; propylene carbonate; pro than gum, Xylitol; Zarzarol; Zein: Zeolex, Zinc, Zinc acetate, pylene glycol alginate, diacetate, dicaprylate, monolaurate, carbonate, chloride, oxide, Stearate, and Sulfate, and other monostearate, palmitostearate, and ricinoleate; propylpara Zinc compounds, and other agents used to dissolve, dilute, ben; prosolv 50, 90, Smcc 50 and 90; protamine sulfate; bind, fill, disintegrate, lubricate, emulsify, carry, Suspend, protein hydrolysate; and pVn/macopolymer. acidify, alkalinize, buffer, solubilize, clarify, gel and/or 0135 Also, quaternium-15 and 52; quatrimycin hydro thicken, enhance viscosity, coat, antioxidize, chelate, stabi chloride; quso f-22; ra-2397; ra-3011; rhodigel-23; rosin; lize, modify release, and/or preserve the product. saccharin; saccharin calcium and sodium; safflower oil; satialgine h; SD alcohol 3a, 40, 40-2, 40b; sea spen; serine; 0140. To the extent that the foregoing lists employ trade names, it is believed that each listed trade name is well known sesame oil; shellac; shellac p.V.p. Solution no. 4; silicon; in the industry and satisfactorily defined in the literature. The silicon dioxide; silicone; silicone emulsion; simethicone; foregoing lists of excipients were generated from the U.S. simethicone c and mdx4-4036; sipon 1-20; and Soap. Food and Drug Administration's Center for Drug Evaluation 0136. Also, sodium acetate, alginate, alkyl Sulfate, ami and Research's database of inactive ingredients present in nobenzoate, ascorbate, benzoate, bicarbonate, bisulfate, FDA-approved drugs. See http://www.fda.gov/cder/iig/IIG bisulfite, bitartrate, borate, borate decahydrate, carbonate, carbonate decahydrate, carbonate hydrate, carboxymethyl download.htm (accessed Nov. 27, 2007). “The Inactive Ingre betaglucan, caseinate, cellulose, cetearyl Sulfate, chlorate, dients Database provides information on inactive ingredients chloride, chlorite, cholesteryl Sulfate, citrate, cocoyl sarcosi present in FDA-approved drug products. This information nate, cyclamate, cysteinate hydrochloride, desoxycholate, can be used by industry as an aid in developing drug prod dithionite, dodecyl benzene sulfonate, formaldehyde Sul ucts.” http://www.fda.gov/cder/iig/iigfacqWEB.htm#what is foxylate, gluconate, hexametaphosphate, hydroxide, active ing (accessed Dec. 4, 2007). Further information on hypochlorite, iodide, lactate, laureth Sulfate, lauroyl sarcosi various ingredients can be found in various resources known nate, lauryl Sulfate, lauryl Sulfoacetate, metabisulfite, nitrate, to those of ordinary skill in the art, including on the Internet phosphate, phosphate dihydrate, polyacrylate, propionate, at: http://www.usactives.com/Z2/index.html (accessed Dec. pyrophosphate, pyrrolidone carboxylate, starch glycolate, 4, 2007). Stearate, Stearyl fumarate. Succinate, Sulfate, Sulfate decahy drate, Sulfite, tartrate, thioglycolate, thiomalate, thiosulfate, Solid Dose Excipient Modules trimetaphosphate, and Xylenesulfonate, and other sodium 0.141. One possible use for solid dose excipient modules is compounds. to add volume to the API module(s) used in the final drug 0.137 Also, SOLULAN; SOMAY 44; sorbic acid; sorbi product. For example, one final drug product may use two tan monolaurate, monooleate, monopalmitate, monostearate, API modules, and a second final drug product may use four sesquioleate, and trioleate; sorbitol; Sorbitol anhydride; soy API modules each having the same volume. To minimize bean flour and oil; Spearmint; spermaceti; Spirits of turpen costs, a standard-sized capsule may be used for both final tine; squalane; Stannous chloride, fluoride, octoate, and tar drug products, with the space remaining after the contents of trate; starch; starch 21, 825,826, 1500 pregelatinized, 1551, the API modules are inserted filled by one or several excipient and 7150; starch aluminum octenyl Succinate; Stearalkonium modules. The size (volume) of such solid dose excipient chloride; stearamidoethyl diethylamine; steareth-2, 10, 20, modules may be determined by analysis of the volumes of the 21 and 100; Stearic acid; Stear-o-wet c.; Stear-o-wet m; Stear portfolio of solid dose API modules and the total volumes of oxytrimethylsilane; Stearoyl polyoxylglycerides; Steartrimo the final formulation(s) (e.g., capsules) used. A variety of nium hydrolyzed animal collagen; Stearyl alcohol and citrate; analytic methods can be used, ranging from trial and error Strawberry; Succimer, Succinic acid; Sucralose. Sucrose; number Substitution to proprietary Software applications, but Sucrose distearate, palmitate, polyesters, Stearate, and syrup; a relatively efficient method is to simply use equation-solving Sugar confectioners; Sugar fruit fine; Sulfacetamide Sodium; Subroutines available in commercial spreadsheet applica sulfur dioxide; sulfuric acid; sulfurous acid; SURELEASE tions. e-719010 clear; SURELEASE e-7-7050: SURFACTOL qs: 0142. Once the volumes are selected, the components are SYNCHRON oral carrier, SYNCHRON oral carrier base kf: developed. These solid dose filler modules may be placebo and SYNCHRON oral carrier vehicle type em. modules composed of granules of coated non-toxic filler, 0138 Also, tagatose; talc: talc triturate; talcum powder; developed with methods known in the art. tall oil; tallow glycerides; tartaric acid; t-butyl hydroperox ide; t-butylhydroquinone; tenox; tenoX-2; terpene resin, tet Liquid Dose Excipient Modules rachloroethylene; tetrofosmin; theophylline; thimerosal; thioglycerol; threonine; thymol; timing Solution clear n-7; 0.143 Multiple types of liquid dose excipient modules can tin, titanium dioxide; tocopherol, tocophersolan; tolu; traga be used. First are taste-masking modules used for oral admin canth; triacetin; tribehenin; tricaprylin; triceteareth-4 phos istration, which contain one or more flavors, Sweeteners, and phate; trichloroethylene; trichloromonofluoromethane; tride other taste-masking agents. A portfolio of taste-masking US 2010/00151.84 A1 Jan. 21, 2010

modules includes several different flavors, both sweet (e.g., ket and business issues are reassessed and a Go or No-go cherry, orange, grape, etc.) and non-Sweet. decision reached, in Some embodiments. 0144) Modules with colorants can be useful to add to taste 0150. When the active ingredient in the prospective API cues as well as assist final drug product differentiation. For module is new to the portfolio, additional evaluation may be example, a patient who is required to take one medication or required. First, the dose/concentration and excipients in the mixture in the morning, and a different medication or mixture API module can be selected as outlined before. Next, the in the evening, can, in addition to different labels, have the portfolio of excipient modules can be matched to the prospec medications customized into different colors, one for morn tive API module to assess whether a new excipient module is ing and the other for evening. Some final drug products opti required. If not, the cost estimates can be used in conjunction mally have no color, because it is unnecessary or creates with the market analysis to reach a Go or No-go decision. potential problems (e.g., dye sensitivity), and separation of 0151. If one or more new excipient modules are needed to color modules enhances this flexibility. A limited number of complement the prospective API module, the components colorants with maximum compatibility are selected, in some selected for the API module may be reevaluated to assess embodiments. whether changes in those components can eliminate the need 0145 Modules with viscosity agents may be used to for some or all of the new excipient module requirements. If modify the thickness of the final product to affect swallowing So, the dose/concentration and excipients in the API module and mouthfeel. Thicker liquids can be used for patients who can be modified. If not, the components of the excipient have difficulty swallowing by slowing the transit of the liquid module(s) may be selected as outlined before. in the mouth and pharynx. On the other hand, thin liquids 0152 Once the new excipient module is designed, it can be could be needed if the drug product is administered by feed evaluated in the context of the entire module portfolio to ing tube. Separation of the Viscosity agent modules enhances determine whether there are opportunities for the module to this flexibility. A limited number of viscosity agents with be used in conjunction with existing modules. If not, the maximum compatibility may be selected. components selected for the excipient module may be 0146 Modules with preservatives or antiseptics are useful reevaluated to assess whether changes in those components if the final drug product is intended for multiple dose use, or can open new opportunities for Synergy. Finally, the cost for longer shelf life. These excipients, however, may compli estimates for both the prospective API module plus any addi cate manufacturing due to poor Solubility or interference with tional needed excipient modules may be used to reassess the analytic methods, and consumers often prefer preservative business issues and a Go or No-go development decision can free preparations. Many modular products can be unit doses be reached. and/or intended for very short storage periods. Thus, separa 0153. Prospective new excipient modules can be similarly tion of preservative modules enhances the flexibility to elimi assessed against the entire current portfolio to optimize com nate these from the final drug product. A limited number of ponent selection and maximize opportunities for synergistic preservatives with maximum compatibility can be selected. use. In a given module development endeavor, an iterative 0147 Simply developing a module for every possible process may be used for designing and assessing potential excipient would be possible, but would be expensive and module characteristics. might provide little advantage over current development and manufacturing techniques. To achieve cost and manufactur Module Selection for Customized Final Drug Assembly ing benefits, the range of possible modules may be pruned to 0154 FIG. 5 summarizes the process of selecting modules match the requirements of the portfolio of APIs and final for final drug product assembly, in one embodiment of the product characteristics (e.g., color, viscosity) desired (see present invention. The selection of modules for assembly of a Module Portfolio Management below). final drug, customized for the user's needs and preferences, can be straightforward. The first API module can be selected Module Portfolio Management based on the needed active ingredient. The number of those 0148 FIG. 4 Summarizes the process of managing a port modules determines the dose of the final product, which can folio of modules, in one embodiment of the present invention. be customized in accordance with the user's physical and Once portfolios of API and excipient modules have been clinical characteristics, age, and, in the case of animals, the developed, the process of adding new modules may be com species and breed. Physical characteristics that can be used to plex. Unlike current development and manufacturing tech customize the dose include weight, mass, and other Volumet niques, where drug products are relatively independent ric measures, skin Surface and other area measures, and per except for marketing concerns, the selection of new modules centage body fat or lean mass and other body composition may be highly dependent on the existing portfolio of mod measures. Clinical characteristics that can be used to custom ules. ize the dose include the user's metabolism, hepatic (liver) 0149 When a potential new API module is identified, one function, and renal (kidney) function that are measured by possible consideration is whether the module contains an clinical/veterinary laboratory testing. additional active ingredient. Some new API modules will 0155 If additional active ingredients are needed, the mod simply add an additional dose or concentration of an existing ule portfolio may be searched for an API module with the active ingredient to the portfolio. In this case, if the dose/ appropriate active ingredient that is compatible with the first concentration is inside the range of existing modules, devel API module (see below for a discussion of compatibility opment is generally straightforward, using existing data and determination). If none is found, and an alternative API mod formulation knowledge. When the dose? concentration is out ule is not available for the first active ingredient, the desired side the range of existing modules, additional information final drug combination may not be possible with the existing about analytical methods, formulation, and manufacturing portfolio. For portfolio management purposes (see above), may be developed or found in public records. Once these the information about the desired final drug product may be issues are defined, and full cost estimates generated, the mar forwarded to R&D to generate a prospective API module. US 2010/00151.84 A1 Jan. 21, 2010

0156 If a compatible combination of API modules is modules, in some embodiments. Linking to the Internet available, the number of each API module may be set as allows health professionals or consumers to customize and described above in an iterative process until all active ingre order the final drug product, in other embodiments. dients are selected. If the API modules are for a solid dose 0163 The ordering and fulfillment process can occur in formulation, the final product form (e.g., capsule) and size multiple ways. Physicians, veterinarians, and other health can be selected according to methods known in the art and the professionals with prescribing privileges can access the data appropriate number of excipient (e.g., filler) modules chosen base by the Internet and select the active ingredient(s), dose to fill any empty space. The final drug product can be (S), form, and other characteristics of the final drug product, in assembled immediately, or the modules packaged together as some embodiments. The prescription can be forwarded elec a final drug package for later assembly into a final drug tronically to either a pharmacist or the patient/consumer, who product. can order and purchase the drug using methods known in the 0157. If the API modules are for a liquid dose formulation, art. Once ordered, the drug product can be packaged and compatible excipient modules can be selected. Generally, the shipped to the patient/consumer, either directly or via the taste-masking module may be chosen first, followed by com pharmacist. patible colorant, Viscosity, and preservative modules as and if 0164. Alternatively, the consumer can access the database needed. The final drug product can be assembled immedi by the Internet and select the active ingredient(s), dose(s), ately, or the modules packaged together for later assembly. form, and other characteristics of the final drug product, in 0158. In both solid and liquid dose formulations, if neces other embodiments. Non-prescription and nutritional prod sary excipient modules are not available, and the API and/or ucts can be ordered and purchased by the consumer, and other excipient modules cannot be adjusted to create a com shipped directly to him. The consumer can also initiate the patible combination, the information about the desired final fulfillment process by forwarding the desired drug and/or drug product may be forwarded to R&D to generate a pro characteristics to a physician, Veterinarian, or other licensed spective excipient module. professional for approval and prescription. 0.165 Finally, the customized products can be labeled with Assembly of Modules for Customized Final Drug Product the name, date, and specific time of administration of each dose. Standard multidose containers of capsules or solutions 0159 FIG. 6 summarizes the options for assembling mod are labeled with the dose and frequency of administration ules for the final drug product for one embodiment. Once the (e.g., twice a day). Patients, however, often forget whether API and excipient modules are selected, they can be they have taken the drug, and the standard container gives few assembled into the final drug product in many ways. The clues to assist their memory. Various methods, such as weekly modules can be assembled and labeled immediately, by a pillboxes with multiple compartments, have been developed manual or automated process, and delivered to the user. Or the modules can be packaged together for delayed assembly. to help drug compliance, but all these have deficiencies. Delayed assembly can be by a manual or automated process, Modular precursors, though, allow multiple ingredients and similar to immediate assembly. Alternatively, the modules doses to be combined and taken at once in some embodiments can be packaged into a kit appropriate for consumer assem of the present invention. The consumer's drug can thus be bly. The kit may include directions for assembly including organized by the specific time of administration, rather than compatible home ingredients. Depending on the components by active ingredient, which enhances compliance. and compatibility of the modules, assembly can include mix 0166 Although not required, the invention will be ing the modules with non-pharmaceutical liquids such as fruit described in the general context of computer-executable juices, soft drinks, hot beverages, or other liquids for con instructions, such as program modules, being executed by a Sumption. personal computer. Generally, program modules include rou tines, programs, objects, components, data structures, etc., Quality Control that perform particular tasks or implement particular abstract data types. Moreover, those skilled in the art will appreciate 0160 FIG. 7 summarizes the methods of controlling qual that the invention may be practiced with other computer sys ity, including assessing compatibility and permissible com tem configurations, including hand-held devices, multipro binations of modules, and ordering processes, in one embodi cessor Systems, microprocessor-based or programmable con ment of the present invention. Sumer electronics, network PCs, minicomputers, mainframe 0161 Specific modules, whether API or excipient, can be computers, and the like. The invention may also be practiced manufactured in a batch process and quality may be tested in distributed computing environments where tasks are per using analytic methods and stability protocols known to the formed by remote processing devices that are linked through art. The data from quality testing, as well as public and pro a communications network. In a distributed computing envi prietary chemical, pharmaceutical, medical and Veterinary ronment, program modules may be located in both local and information about the various components of the modules and remote memory storage devices. U.S. Pat. No. 7.243,299, their interactions, may be used to guide and refine module which is incorporated herein by reference, includes a detailed design and development. And that knowledge may be further description of a conventional general-purpose digital com used to refine module manufacturing and create a computer puting environment that can be used to implement various database of permitted combinations of modules. aspects of the invention. 0162 The database of permitted combinations of modules 0167. In some embodiments of the present invention, can be maintained on a computer and may be linked to both an methods of selecting one or more API modules and one or ordering application and the Internet or other computer net more excipient modules, and manufacturing final drug pack work. Integration of the database and ordering application ages and final drug products are performed by computer enhances quality by controlling the assembly of the final drug executable instructions stored on one or more computer-read products and preventing the combination of incompatible able media. Computer-readable media are any suitable media US 2010/00151.84 A1 Jan. 21, 2010 that can store data, including instructions, that are accessible thereof. Such systems, in some embodiments, are adaptable by a computer. Computer-readable media, such as hard disks, to combine a fixed amount of at least one API with another removable magnetic disks, removable optical disks, magnetic fixed amount of at least one excipient, to make at least one API cassettes, flash memory cards, digital versatile disks, Ber module. Other embodiments provide systems to isolate a noulli cartridges, random access memories (RAMs), read fixed amount of at least one excipient to make at least one only memories (ROM), and the like, may be used in some excipient module. In still other embodiments, such systems embodiments of the present invention. are adaptable to combine a fixed amount of one excipient with another fixed amount of another excipient to make at least one 0168 A "computer' includes any suitable machine. Such excipient module. Yet other embodiments are adaptable to machines include, but are not limited to, desktop computers, deliver the contents of the module to a container. The system lap top computers, palm top computers, PDAs, cellular tele can be a manual system, an automated system, or a partially phones, media players (such as, for example, iPODS and automated system. In some embodiments, the system is KINDLES), servers, dedicated apparatus such as equipment capable of determining one or more fixed amounts based on adapted to manufacture one or more of modules, final drug instructions received. packages, and final drug products, and the like. In some 0172 Some embodiments of the present invention com embodiments, a computer includes more than one machine prise means for storing compatibility information for each working in concert with another. Examples of multiple API module and each excipient module. In some of those machines working together include, but are not limited to, a embodiments, a given module has associated compatibility PDA accessing a database stored on a server through a broad information, such as which APIs, excipients, API modules, band connection via the Internet; a terminal accessing a main and/or excipient modules are compatible with the given mod frame computer; and a desktop computer accessing a net ule. In other embodiments, compatibility information con work of other computers. tains concentration information, such as the relative amount (0169 Computer-executable instructions and computer of an excipient needed to solubilize a given amount of an API. executable components appearing in some embodiments of Such means include any suitable means for storing informa the present invention include software programs, operating tion. In some embodiments, means for storing compatibility Systems, applications, subroutines, data structures, and the information are chosen from paper records, computer-read like. Such instructions and components may be stored on a able records, and combinations thereof. Computer-readable single memory device, or on many memory devices, and may records can be stored on computer-readable media. In still be local (e.g., on a single computer), distributed (e.g., on more other embodiments, various modules are classified for easy than one computer), remote (e.g., accessed through a network formulation. For example, all modules in a given class can be or the Internet), or a combination thereof. Similarly, those considered compatible, and therefore may be readily com instructions and components can be operated locally, in a bined to form a final drug product. In other embodiments, distributed manner, remotely, or a combination thereof. For several classes are used. example, one computer in a doctor's office could correlate (0173 It is contemplated, for some embodiments of the patient information including one or more of diagnosis, pre present invention, that proprietary information will be devel Scription, age, weight, gender, allergy information, and aes oped regarding, for example, the composition, amounts, and thetic preferences with one or more remote computer systems compatibility of API modules and excipient modules. In other that contain API module information and excipient module embodiments, at least some data will be generated in an open information to develop a final drug product. Source code fashion, whereby physicians, pharmacists, (0170 A system for manufacturing at least one final drug manufacturers, and/or patients develop and share expertise product, at least one final drug package, or both, in some about compatibility among APIs, excipients, API modules, embodiments, comprises at least one API module portfolio and/or excipient modules. For example, new compatibility and at least one excipient module portfolio, in which the information can be recorded, stored, updated, and consulted portfolios are operatively connected to manufacture the final in a widely-accessible forum, such as one or more websites on drug product or final drug package. In some embodiments, the Internet to assist others to formulate new embodiments of “operatively connected to manufacture the final drug product the invention. In some embodiments, such a forum is peer or final drug package” means the system is capable of follow reviewed and managed by knowledgeable professionals who ing instructions for selecting a number of API modules from ensure the integrity of the information. In other embodiments, the API module portfolio, and selecting a number of excipient the forum allows patients to provide their anecdotal evidence modules from the excipient module portfolio to form the final and experience about the compatibility of various final drug product or package. In some embodiments, the system can packages and final drug products they have used. Profession form a single dose or multiple doses from the selected mod als and patients alike can consult such forums to assist the ules. The system, in other embodiments, comprises one or development of new modules, new portfolios, new final drug more module storage facilities, optionally one or more mod packages, and new final drug products. Some embodiments of ule packaging structures for making a final drug package, and the present invention provide computer-executable instruc optionally one or more module content combination means tions for consulting such forums during the development of for making a final drug product. The system can be a manual new portfolios, new modules, new final drug packages, and System, an automated system, or a partially automated sys new final drug products. tem. In other embodiments, the system is capable of deter mining the number of various modules necessary to formulate EXAMPLES a final drug product, or to assemble a final drug package, Example 1 based on inputted prescription information. Customizing Formulation Type for a Pediatric (0171 Other embodiments of the present invention provide Patient Systems and methods for manufacturing one or more API (0174. A 5 year old male is seen by is pediatrician and modules, one or more excipient modules, or a combination diagnosed with spasticity from cerebral palsy. The spasticity US 2010/00151.84 A1 Jan. 21, 2010

is not controlled by the standard, first-line drug, which is ing hypertension, hypercholesterolemia, heart disease, and available in an oral liquid formulation. The physician plans to diabetes, and is on eight different medications. The patient's add a second antispastic drug, but this drug is only available blood pressure is high, and he complains to his physician that in a tablet formulation and the patient is notable to swallow he is having a hard time keeping track of all the medications. tablets. The physician then prescribes a customized final drug Upon checking, the physician discovers that the patient product that is an oral liquid. First, he accesses the API mod neglected to fill one prescription for hypertension. The phy ule database via the Web and confirms that the desired active sician accesses the module database and learns that 6 of the 8 pharmaceutical ingredient is available. After selecting the prescribed drugs are available in API modules. Following an appropriate API module and dose, he follows software-pro interactive interface he selects the six APIs, indicates the vided prompts to select the excipient modules necessary desired dosage, and is presented with the option of combining (Sweetener and flavor-enhancer, colorant, preservative, vis three of the medications into one daily capsule, and combin cosity agent, and additional carrier) to complete the formula ing the other three drugs into another capsule taken twice a tion. He knows the child hates cherry, so he selects a grape day. The two customized prescriptions are generated, which flavor instead. A customized prescription is generated detail simplify the patient's drug regimen from a total of 15 tablets ing the number of each specific module, and is signed and taken at three different times of the day, to only four tablets at filed electronically with an appropriate facility for final breakfast and two more at dinner. The two remaining pre assembly and delivery to the patient. scribed drugs, for which API modules are not yet available, Example 2 are taken in conventional form. Customizing Dose in an Elderly Patient Example 5 0.175. A 96 year-old female is seen by her gerontologist and diagnosed with depression. This has occurred before, and Preventing Drug Incompatibilities in a Hospitalized the physician plans to prescribe an antidepressant. In the past, Patient the patient has been very sensitive to the sedative effects of the preferred antidepressant, but she solved the problem by split 0.178 A 58 year-old female is admitted to Hospital A with ting the lowest available dose tablets. Now, however, the advanced breast cancer for a course of chemotherapy with patient's eyesight and dexterity have deteriorated to the point three agents. At the same time another patient is admitted to where splitting tablets is unsafe. In addition, the physician Hospital B for the same, well accepted but relatively rare believes it is likely the patient's sensitivity has increased due treatment plan. As standard practice, all three chemotherapy to continuing decline in her liver function. Following the agents are sequentially attached to the same intravenous line. same procedure as in Example 1, the physician prescribes a Unbeknownst to the hospitals or medical professionals, how customized drug that includes the desired active ingredient in ever, the manufacturer of one chemotherapy agent has a capsule with one quarter of the lowest commercially avail changed its formulation slightly to use a different excipient. able dose. The customized prescription is generated and sent The new formulation is well tested for compatibility with to a local pharmacy for final assembly, and the patient is able frequently used treatment protocols and approved by the FDA to pick up the medication later that day. Two weeks later, the because it stabilizes the active ingredient and permits alonger patient reports less than optimal improvement, and since she shelf life. It has not, however, been tested with the treatment is not experiencing any sedative side-effects, the physician protocol planned for these two patients. changes the customized drug to one containing 35% of the 0179. In Hospital A, where each drug is purchased sepa lowest dose available commercially (a dose that would be rately, when the chemotherapy is administered, the new for impossible to duplicate with tablet splitting). mulation interacts with the other, unchanged agents, and pre Example 3 cipitates, causing severe complications. In Hospital B all multiagent treatments are customized using precursor mod Customizing Excipients to Minimize Allergic Reac ules and assembled in the hospital's pharmacy. When the tion desired agents are selected, the potential incompatibility is 0176 A 47 year-old female is seen by her gynecologist highlighted as an untested combination. The pharmacist is and diagnosed with vaginal bacteriosis. The physician plans given a choice of including the older version of the API to prescribe a topical cream, but the patient is allergic to the module in a triple combination, or to generate two customized commercially available formulation, specifically, the Viscos drugs with instructions that prevent concurrent administra ity agent used to enhance the creaminess of the product. The tion of the new version of the API module. The older version physician then prescribes a customized drug that includes the in triple combination is selected, and the patient has an excel desired active ingredient, but without the allergen. The phy lent response. sician accesses the module database and selects the appropri ate modules following the same procedure as in previous INDUSTRIAL APPLICABILITY examples. In this case, a formulation is possible without any Viscosity agent at all. The physician's office maintains a drug 0180. Some embodiments of the present invention relate assembly kiosk for patient convenience, and since all needed to the manufacture of medicaments useful for treating one or API modules and excipient modules are on hand, the patient more diseases, disorders, and conditions in one or more is able to leave the office with her medication. human and animal patients in need thereof. In some aspects, the present invention improves on conventional methods of Example 4 manufacturing drugs, which depend on economies of scale. Simplifying a Medication Regimen in an Elderly Those economies of Scale require relatively large patient Patient populations, because the regulatory burdens of bringing a 0177. A 75 year-old male is seen by his internist in a new drug to market render so-called “orphan drugs' eco follow-up visit. He has numerous medical problems, includ nomically infeasible. Accordingly, Some embodiments of the US 2010/00151.84 A1 Jan. 21, 2010 19 present invention provide economically viable means to 8. A final drug product, made by a process comprising: manufacture final drug products for underserved patient combining at least one API module comprising at least one populations. active pharmaceutical ingredient, and at least one excipient module, to make the final drug product; 0181. In other aspects, the present invention industrializes so-called formulary pharmacy, in which a pharmacist formu wherein the at least one active pharmaceutical ingredient is lates a prescribed medicine for an individual patient. Formu present in the final drug product in an amount effective lation accuracy, potency preservation, contaminant and for treating at least one disease, at least one disorder, at microbial control, and shelflife are greatly enhanced over that least one condition, or a combination thereof, in at least achievable by formulary pharmacy in some embodiments of one human or animal patient in need thereof. the present invention. Moreover, individual patients and 9. A final drug package, comprising: health care providers are given much greater control over the at least one API module, which comprises medicines, vitamins, botanicals, nutraceuticals, and other at least one first excipient, and Substances to be consumed for health purposes. at least one active pharmaceutical ingredient; and 0182 While the invention has been particularly shown and at least one excipient module, which comprises described with reference to preferred embodiments thereof, it at least one second excipient; will be understood by those skilled in the art that various wherein the at least one second excipient is compatible changes in form and details may be made therein without with the at least one active pharmaceutical ingredient; departing from the spirit and scope of the invention. Further wherein the at least one active pharmaceutical ingredient is more, the foregoing description of various embodiments does present in the final drug package in an amount effective not necessarily imply exclusion. For example, "some for treating at least one disease, at least one disorder, at embodiments may include all or part of “other and “further least one condition, or a combination thereof, in at least embodiments within the scope of this invention. one human or animal patient in need thereof, and What is claimed is: wherein the at least one API module and the at least one 1. A method for manufacturing a final drug product, com excipient module are adapted to form a final drug prod prising: uct. Selecting a first API module comprising 10. An API module, comprising: at least one first active pharmaceutical ingredient and at least one excipient in a first fixed amount, and at least one first excipient; at least one active pharmaceutical ingredient in a second determining a number of the first API module: fixed amount of at least a dose escalation interval or a choosing a first excipient module comprising fraction thereof. at least one second excipient; 11. The API module of claim 10, wherein the second fixed determining a number of the first excipient module; and amount is greater than the dose escalation interval. combining the number of the first API module and the 12. The API module of claim 10, wherein the second fixed number of the first excipient module to manufacture the amount is less than a dose of the at least one active pharma final drug product. ceutical ingredient. 2. The method of claim 1, wherein: 13. The API module of claim 12, wherein the second fixed the number of the first API module is greater than one. amount is less than the minimum dose of the at least one 3. The method of claim 2, wherein: active pharmaceutical ingredient. the number of the first API module is greater than five. 14. The API module of claim 13, wherein the second fixed 4. The method of claim 1, implemented by computer-ex amount is less than about 80% of the minimum dose of the at ecutable instructions stored on one or more computer-read least one active pharmaceutical ingredient. able media. 15. An excipient module, comprising: 5. The method of claim 1, further comprising: Selecting a second API module comprising at least one first excipient in a first fixed amount; and at least one second active pharmaceutical ingredient and at least one second excipient in a second fixed amount; at least one third excipient; wherein the at least one first excipient and the at least one determining a number of the second API module: second excipient are compatible with at least one active combining the number of the second API module with the pharmaceutical ingredient. number of the first API module and the number of the 16. The excipient module of claim 15, wherein the at least first excipient module to manufacture the final drug one first excipient and the at least one second excipient are product. compatible with two or more active pharmaceutical ingredi 6. The method of claim 5, further comprising: entS. Selecting a second excipient module comprising 17. A system for manufacturing at least one final drug at least one fourth excipient; product, at least one final drug package, or both, comprising: determining a number of the second excipient module; and at least one API module portfolio comprising a plurality of combining the number of the second excipient module different API modules; and with the number of the second API module, the number at least one excipient module portfolio comprising a plu of the first API module, and the number of the first rality of different excipient modules: excipient module to manufacture the final drug product. wherein the at least one API module portfolio and the at 7. The method of claim 5, implemented by computer-ex least one excipient module portfolio are operatively con ecutable instructions stored on one or more computer-read nected to manufacture the at least one final drug product, able media. the at least one final drug package, or both. US 2010/00151.84 A1 Jan. 21, 2010 20

18. The system of claim 17, further comprising one or more a computer-executable component for providing one or means for storing compatibility information for at least one more of compatibility information, dose information, API module and at least one excipient module. and dose escalation interval information for at least one API module; and 19. A computer-readable medium having computer execut a computer-executable component for providing compat able components implementable in a system operable to ibility information for at least one excipient module. manufacture at least one final drug product, at least one final drug package, or both, comprising: c c c c c