US 20160279056A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0279056A1 Zhao et al. (43) Pub. Date: Sep. 29, 2016 (54) LIQUISOFT CAPSULES Publication Classification (71) Applicant: BANNER LIFE SCIENCES LLC, (51) Int. Cl. High Point, NC (US) A6IR 9/00 (2006.01) A 6LX 9/50 (2006.01) (72) Inventors: Yinyan Zhao, Greensboro, NC (US); A63L/46.5 (2006.01) Yunhua Hu, Cary, NC (US); Mervin A6II 3L/28 (2006.01) Williams, JR., Jamestown, NC (US); A6II 45/06 (2006.01) Tatyana Dyakonov, Greensboro, NC A63L/485 (2006.01) (US); Saujanya Gosangari, Jamestown, (52) U.S. Cl. NC (US); Chue Yang, Greensboro, NC CPC ............. A61K 9/0056 (2013.01); A61K 45/06 (US); Henricus Marinus, Gerardus, (2013.01); A61K 31/485 (2013.01); A61 K Maria Van Duijnhoven, den Bosch 3 1/465 (2013.01); A61 K3I/28 (2013.01); (NL); Martin Piest, Tilburg (NL); A61K 9/5057 (2013.01); A61K 9/5052 Aqeel A Fatmi, High Point, NC (US) (2013.01); A61K 9/5089 (2013.01) (57) ABSTRACT (21) Appl. No.: 15/080,614 Described herein are oral pharmaceutical compositions Suit able for chewing, Sucking, or buccal dissolution comprising (22) Filed: Mar. 25, 2016 Soft gel capsules and liquid fills, methods for making the same, and methods for treating Subjects in need thereof with Related U.S. Application Data Such capsules. In particular, oral pharmaceutical composi (60) Provisional application No. 62/236,297, filed on Oct. tions comprising chewable. Suckable, or dissolvable soft gel 2, 2015, provisional application No. 62/138,468, filed capsules with various flowable fill compositions are on Mar. 26, 2015. described. Patent Application Publication Sep. 29, 2016 US 2016/0279056A1 FIGURE 1 120 1OO 60 40 O 2O 40 60 Time (min) US 2016/0279056A1 Sep. 29, 2016 LIQUISOFT CAPSULES properties that can be sucked or that slowly dissolve in the mouth to release pleasant-tasting or refreshing liquid fills. CROSS REFERENCE TO RELATED APPLICATIONS SUMMARY 0001. This application claims priority to U.S. Provisional 0008. One embodiment described herein is an oral phar Patent Application Nos. 62/138,468, filed on Mar. 26, 2015, maceutical composition Suitable for chewing, Sucking, or and 62/236,297, filed on Oct. 2, 2015, each of which is buccal dissolution comprising a soft capsule with a flowable incorporated herein in its entirety by express reference fill comprising one or more active pharmaceutical ingredi thereto. This application is related to International Patent ents, nutraceuticals, flavors, or refresheners. Exemplary Application No. PCT/US2016/ , filed on Mar. 25, embodiments are cough and cold over-the-counter (OTC) 2016, which is incorporated herein in its entirety by express remedies; nonsteroidal anti-inflammatory drugs (NSAIDs) reference thereto. for treating pain; nicotine satiation, nicotine-replacement therapy, or Smoking cessation therapy; breath fresheners or TECHNICAL FIELD treatments for halitosis; treatments for temporary discom forts of the stomach and gastrointestinal tract; or as a 0002. Described herein are oral pharmaceutical compo delivery means for any of the active pharmaceuticals sitions suitable for chewing. Sucking, or buccal dissolution described herein. comprising soft gel capsules and liquid fills, methods for 0009. Another embodiment described herein is an oral making the same, and methods for treating Subjects in need pharmaceutical composition Suitable for chewing, sucking, thereof with Such capsules. In particular, oral pharmaceuti or buccal dissolution comprising a shell encapsulating a cal compositions comprising chewable. Suckable, or dissolv matrix, the shell comprising: (a) one or more film-forming able softgel capsules with various flowable fill compositions polymers; (b) one or more plasticizers; (c) one or more are described. polymer modifiers; (d) one or more first Sweeteners; (e) one or more first solvents, (f) optionally, one or more excipients; BACKGROUND and a matrix comprising: (g) one or more hydrophilic 0003 Chewable dosage forms are typically manufactured vehicles: (h) one or more flavors: (i) one or more second as Solids, such as chewable tablets, or elastic semi-solids Sweeteners; () one or more second solvents; (k) one or more Such as chewing gums, molded gels, or chewable soft gelatin active pharmaceutical ingredients; and (1) optionally, one or capsules. While elastic semi-solid forms provide better more excipients. In one aspect describe herein, the film mouth feel and customer acceptance, chewable soft gelatin forming polymer comprises one or more of gelatin, partially capsules (e.g., "soft gels') have a benefit of being ingestible hydrolyzed gelatin, hydrolyzed gelatin, hydrolyzed colla and can deliver accurate amounts of active ingredients to the gen, or combinations thereof. In another aspect describe oral cavity and digestive system. herein, the plasticizer comprises one or more of glycerol, maltitol, mannitol. Xylitol, lycasin, or combinations thereof. 0004 Soft gels have gained popularity and acceptance In another aspect describe herein, the polymer modifier due to their elegant and clear gelatin shells. Furthermore, comprises one or more of citric acid, acetic acid, lactic acid, softgel capsules are uniform, stable, dissolve quickly, allow malic acid, tartaric acid, or combinations thereof. In another for liquid formulations, and are easier for most Subjects to aspect describe herein, the hydrophilic vehicle comprises swallow. propylene glycol, polyethylene glycol 400, polyvinylpyr 0005 Soft gel capsules are typically formed of a capsule rolidone K30, glycerin, sorbitol, xylitol, maltitol, or combi shell encapsulating a liquid matrix fill. Several types of soft nations thereof. In another aspect describe herein, the first gel capsules can be chewed by the user. See e.g., U.S. Pat. Sweetener comprises sucralose, aspartame, Stevia, acesul Nos. 6,258,380; 8,097,279; 8,241,665; 8,414,916; and fame potassium, Xylitol, or combinations thereof. In another 8.765,174. Such chewable soft capsules are chewed by the aspect describe herein, the flavoring comprises citric acid, subject to release the fill contents into the mouth, instead of lactic acid, sodium citrate, orange flavor, eucalyptol, pep swallowing the capsule with the fill still encapsulated within permint oil, methyl salicylate, glycine, or combinations the shell. Often the fill of chewable soft capsules contains thereof. In another aspect describe herein, the second sweet Substantial amounts of gelatin giving the fill a semi-solid ener comprises mannitol, maltitol, Xylitol, thaumatin, gly characteristic, rather than a true liquid character. cyrrhizic acid salts, acesulfame potassium, acesulfame salts, 0006 Although chewable soft capsules provide an effec Sucralose, aspartame, Stevia, or combinations thereof. In tive dosage system, user acceptance has been limited by the another aspect describe herein, the active pharmaceutical organoleptic properties of the capsules, which are some ingredient comprises one or more of astemizole, azelastine, times criticized as being leathery or rubbery. Chewable soft aZatadine, brompheniramine, carbinoxamine, cetirizine, capsules sometimes have a distinguishable difference chlorpheniramine, clemastine, cyproheptadine, deslorata between the shell and fill in terms of texture and mouth-feel. dine, dexbrompheniramine, dexchlorpheniramine, diphen Some users experience difficulty consuming the masticated hydramine, fexofenadine, hydroxy Zine, levocetirizine, lor sheath after the internal fill has been released. In addition, atadine, phenindamine, pheniramine, phenyltoloxamine, chewable soft capsules tend to harden over time. promethazine, pyrilamine, terfenadine, tripelennamine, 0007 Thus, there is an unmet need for chewable soft triprolidine, acetyl dihydrocodeine, benproperine, benzona capsule dosage forms comprising liquid fills, where the tate, benzylmorphine, bibenzonium bromide, butamirate, capsule shell can be chewed. Sucked, or that dissolves in the butorphanol, carbetapentane, chlophedianol, clobutinol, mouth and releases the active ingredient in a liquid form in clofedanol, cloperastine, codeine, dextromethorphan, dex the oral cavity. Accordingly, it is desirable to develop tromethorphan hydrobromide, diacetylmorphine, dibunate, chewable soft gelatin capsules having desirable organoleptic dihydrocodeine, dimemorfan, dimethoxanate, diphenhy US 2016/0279056A1 Sep. 29, 2016 dramine, dropropizine, droxypropine, ethylmorphine, fedri choline magnesium salicylate, diclofenac, diflunisal, etod late, glaucine, hydrocodone, hydromorphone, isoaminile, olac, etoricoxib, faislamine, fenbufen, fenoprofen, flurbipro laudanum, levodropropizine, levomethadone, levopropoxy fen, indometacin, ketoprofen, ketorolac, lornoxicam, loXo phene, meprotixol, methadone, morclofone, nepinalone, profen, meloxicam, meclofenamic acid, mefenamic acid, nicocodine, nicodicodine, normethadone, noscapine, oxela meloxicam, metamizole, methyl salicylate, magnesium din, oxolamine, pentoxyverine, pholcodine, pipaZetate, pip salicylate, nabumetone, naproxen, nimeSulide, paracetamol. eridione, prenoxdiazine, tipepidine, Zipeprol, acetylcysteine, oxyphenbutaZone, parecoxib, phenylbutaZone, piroxicam, althea root, ambroXol, antimony pentasulfide, bromhexine, salicyl salicylate, Sulindac, Sulfinpyrazone, Suprofen, tenoxi carbocisteine, cineole, combinations, combinations, creo cam, tiaprofenic acid, tolmetin, Valdecoxib, acetylsalicylic Sote, dembrexine hydrochloride, domiodol, dornase alfa, acid, aloxiprin, aminophenaZone, anilides, benorilate,