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WO 2015/167760 Al 5 November 2015 (05.11.2015) P O P C T

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WO 2015/167760 Al 5 November 2015 (05.11.2015) P O P C T (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/167760 Al 5 November 2015 (05.11.2015) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 9/70 (2006.01) A61K 47/36 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 47/06 (2006.01) A61K 47/38 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 47/30 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, PCT/US20 15/0246 18 KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (22) International Filing Date: MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, 7 April 2015 (07.04.2015) PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (25) Filing Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 61/985,123 28 April 2014 (28.04.2014) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 14/302,830 12 June 2014 (12.06.2014) US TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicant: CELANESE ACETATE LLC [US/US]; 222 DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, West Las Colinas Blvd., Suite 900N, Irving, Texas 75039 LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, (US). SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). (72) Inventors: COMBS, Michael; P. O. Box 794, Pembroke, Virginia 24136 (US). BISSET, Wendy; 391 Briar Patch Declarations under Rule 4.17 : Trail, Eggleston, Virginia 24086 (US). MILWARD, — as to applicant's entitlement to apply for and be granted a Lizbeth; 3000 Richmond Lane Apt. B, Blacksburg, Vir patent (Rule 4.1 7(H)) ginia 24060 (US). LARKIN, Adam; 3700 Cole Avenue, Apt. 430, Dallas, Texas 75204 (US). BUDHAVARAM, — as to the applicant's entitlement to claim the priority of the Naresh; 550 Mt. Zion Rd., Apt. 352, Florence, Kentucky earlier application (Rule 4.1 7(in)) 41042 (US). Published: (74) Agents: KAISER, Iona et al; McDermott Will & Emery — with international search report (Art. 21(3)) LLP, 500 North Capitol Street, N.W., Washington, District of Columbia 20001 (US). © - ¾ (54) Title: DRUG DELIVERY VEHICLES COMPRISING CELLULOSE DERIVATIVES, STARCH DERIVATIVES, AND o- COMBINATIONS THEREOF (57) Abstract: A drug delivery vehicle (e.g., a patch, a pill, an intravaginal ring, and an implant) may include a polymer matrix com- prising a plasticizer and at least one selected from the group consisting of: a cellulose ester, a cellulose ether, a starch ester, a starch ether, and a combination thereof. A drug may be dispersed in the polymer matrix, in another portion of the drug delivery vehicle, or both. DRUG DELIVERY VEHICLES COMPRISING CELLULOSE DERIVATIVES, STARCH DERIVATIVES, AND COMBINATIONS THEREOF BACKGROUND [000 1] The exem plary embodiments described herein relate to drug del ivery vehicles, and methods relating thereto. As used herein, the term "vehicle" refers to a conveyance (e.g. , a patch, a pil l, an intravaginal ring, and an implant) for containing, transporting, and optional ly releasing a desired compou nd . As used herein, the term "drug" refers generical ly to a compou nd that has a biological effect incl uding active pharmaceutical agents, prodrugs of active pharmaceuticals, antifungal compou nds, nutritional supplements, biological compou nds like peptides, and so on. [0002] It is often desira ble and important to provide a sustained release of a drug to patients at a control led rate, which may be ad ministered in a variety of ways including pills for oral administration, patches for transdermal administration, and smal l rods for implantation . I n some instances, drug del ivery over a long period of time is preferred (e.g. , for birth control) . I n other instances, delivery in a local ized area for a relatively short period of time is preferred (e.g. , for wound dressing and treatment). To accompl ish this, different approaches have been used for controlled drug delivery to patients. For example, polymeric compositions may be loaded with drugs, which then diffuse into the patient at the application site. I n many insta nces, the polymeric compositions may incl ude polyurethanes, polyolefins, and ethylene vinyl acetate copolymers. These polymers are general ly considered hydrophobic, which may limit the drug compositions and drug concentrations that may be used therewith due to hydrophil ic/hydrophobic interactions. Therefore, compositions that provide hydrophilic polymeric matrices or may be blended with the hydrophobic polymers may be usefu l for increasing the types of drugs and concentrations of drugs that may be del ivered by a control led diffusion mechanism . BRIEF DESCRIPTION OF THE DRAWINGS [0003] The fol lowing figures are incl uded to illustrate certain aspects of the embodiments presented herein, and shou ld not be viewed as exclusive embodiments. The subject matter disclosed is capable of considerable modifications, alterations, combinations, and equivalents in form and function, as will occur to those skilled in the art and having the benefit of this disclosure. [0004] FIG. 1 illustrates a cross-sectional diagram of a dermal patch. [0005] FIG. 2 illustrates a cross-section of an intravaginal ring. DETAILED DESCRIPTION [0006] The exemplary embodiments described herein relate to drug delivery vehicles that include plasticized cellulose derivatives, plasticized starch derivatives, or both, including methods relating thereto. [0007] Plasticized cellulose derivatives and plasticized starch derivatives may be useful in forming the polymeric matrix of vehicles that deliver drugs to patients. Cellulose derivatives and starch derivatives have been shown to be plasticized with acetylsalicylic acid (aspirin) and other small molecules. I n some instances, high concentrations of the small molecules can be achieved (e.g., 40:60 wt% cellulose derivative or starch derivative to acetylsalicylic acid), which may allow for high loading of a drug in a vehicle. [0008] Further, plasticized cellulose derivatives and plasticized starch derivatives may formulated to be tacky or non-tacky at room temperature, which may allow for the use of plasticized cellulose derivatives and plasticized starch derivatives in various portions of a drug release vehicle. For example, referring to a cross-sectional diagram of a patch illustrated in FIG. 1, tacky compositions may be used as an adhesive 102 for the skin side 104 of the dermal patch 100 where the adhesive may contain a desired drug like nicotine or aspirin. Alternatively, or in combination with such an adhesive, a non-tacky (or less tacky) composition may be used as an intermediate layer 106 between the adhesive and a backing 108 of the dermal patch 100. [0009] Additionally, plasticized cellulose derivatives and plasticized starch derivatives may be compounded with other polymers traditionally used in the production of drug delivery vehicles like ethylene vinyl acetate. Therefore, the compositions of such blends may be used to tailor the release profile of drug delivery vehicles produced therewith. [0010] It should be noted that when "about" is used in reference to a number in a numerical list, the term "about" modifies each number of the numerical list. It should be noted that in some numerical listings of ranges, some lower limits listed may be greater than some upper limits listed. One skilled in the art will recognize that the selected subset will require the selection of an upper limit in excess of the selected lower limit. Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth used in the present specification and associated claims are to be understood as being modified in all instances by the term "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the embodiments described herein. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claim, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. [0011] A drug delivery vehicle described herein may include a polymeric matrix that comprises plasticized cellulose derivatives, plasticized starch derivatives, or both and optionally further comprises other polymers (e.g., ethylene vinyl acetate copolymer and polyurethanes). I n some instances, a polymeric matrix may further include one or more drugs. I n some instances, a plasticizer of the cellulose derivatives or starch derivatives may be a drug. [0012] As used herein, the term "plasticized cellulose derivatives" refers to cellulose derivatives having at least 1% plasticizer by weight of the cellulose derivatives. Cellulose derivatives suitable for use in conjunction with a polymeric matrix described herein may, in some embodiments, have ester substituents that include, but are not limited to, Ci -C2 aliphatic esters (e.g., acetate, propionate, or butyrate), functional Ci -C2 aliphatic esters (e.g., acrylates or diesters) aromatic esters (e.g., benzoate or phthalate), substituted aromatic esters, and the like, any derivative thereof, and any combination thereof.
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