Claims for Patent: 10,195,211

Summary for Patent: 10,195,211

Title:	Soft lozenge compositions
Abstract:	Described herein are topical, non-systemic, slow releasing oral pharmaceutical compositions, methods for making the same, and methods for treating subjects in need thereof with such compositions. In particular, the oral composition provides topical, non-systemic administration of one or more active pharmaceutical ingredients to the oral cavity and upper gastrointestinal track, including the esophagus. In one embodiment, the pharmaceutical composition provides topical corticosteroids to the esophagus and oral cavity.
Inventor(s):	Zhao; YinYan (Greensboro, NC), Hughey; Justin (Asheboro, NC), Vaughn; Jason (Browns Summit, NC), Fang; Qi (Oak Ridge, NC)
Assignee:	Patheon Softgels, Inc. (High Point, NC)
Application Number:	15/795,846
Patent Claims:	1. An oral slow releasing, solid, soft lozenge pharmaceutical dosage form comprising a shell encapsulating a semisolid matrix fill, the shell comprising: (a) about 10% to about 60% by mass of one or more gelatins; (b) about 5% to about 20% by mass of glycerol; (c) about 0.1% to about 5% by mass of citric acid, acetic acid, lactic acid, malic acid, tartaric acid, fumaric acid, or combinations thereof; (d) about 10% to about 80% by mass of one or more of maltitol, xylitol, sucralose or combinations thereof; and (e) about 5% to about 30% by mass of water; and the matrix comprising: (f) about 5% to about 30% by mass of one or more gelatins; (g) about 1% to about 5% by mass of one or more polyethylene oxides comprising a molecular weight of about 900,000 to about 8,000,000; (h) about 5% to about 20% by mass of glycerol; (i) about 0.5% to about 5% by mass of one or more of citric acid, acetic acid, lactic acid, malic acid, tartaric acid, fumaric acid, or combinations thereof; (j) about 10% to about 80% by mass of one of maltitol, xylitol, sucralose, or combinations thereof; (k) about 0.1% to about 1% by mass of polysorbate 20, polysorbate 40, polysorbate 60, or polysorbate 80; (l) about 5% to about 30% by mass of water; and (m) about 0.001% to about 5% by mass of one or more active pharmaceutical ingredients. 2. The composition of claim 1, wherein the composition orally dissolves within about 10 to about 15 minutes upon administration to a subject. 3. The composition of claim 1, wherein the composition contacts the oral and esophageal mucosa for at least about 10 minutes after administration to a subject. 4. The composition of claim 1, wherein the composition contacts the oral and esophageal mucosa for about 10 minutes to about 45 minutes after administration to a subject. 5. The composition of claim 1, wherein the composition achieves about 50% dissolution in vitro at pH 7.4 within about 10 to about 30 minutes. 6. The composition of claim 1, wherein the polyethylene oxide comprises a molecular weight (M.sub.v) of about 7,000,000. 7. The composition of claim 1, wherein the gelatins comprises one or more of gelatin, partially hydrolyzed gelatin, hydrolyzed gelatin, or combinations thereof. 8. The composition of claim 1, further comprising one or more thickening agents comprising polyacrylic acid, methyl cellulose, alginic acid, chitosan, carboxymethyl cellulose, sodium carboxymethyl cellulose, locust bean gum, xanthum gum, or combinations thereof. 9. The composition of claim 1, wherein the active pharmaceutical ingredient comprises one or more corticosteroids. 10. The composition of claim 1, wherein the active pharmaceutical ingredients comprise one or more of fluticasone, budesonide, salts thereof, or combinations thereof. 11. The composition of claim 1, wherein the active pharmaceutical ingredient comprises fluticasone propionate. 12. The composition of claim 1, wherein the active pharmaceutical ingredient comprises about 0.025% or about 0.05% fluticasone propionate. 13. The composition of claim 1, wherein the active pharmaceutical ingredient comprises about 0.5 mg or about 1.0 mg of fluticasone propionate. 14. The composition of claim 1, wherein the matrix further comprises a second active pharmaceutical ingredient. 15. The composition of claim 14, wherein the second active pharmaceutical ingredient comprises lidocaine, prilocaine, or a combination thereof. 16. The composition of claim 14, wherein the second active pharmaceutical ingredient comprises about 0.5% to about 5% by weight of the matrix of lidocaine, prilocaine, or a combination thereof. 17. A pharmaceutical combination comprising the composition of claim 1 and one or more additional therapeutic compounds. 18. The pharmaceutical combination of claim 17, wherein the one or more additional therapeutic compound comprises calcium hydroxide, magnesium hydroxide, alluminum hydroxide, sodium bicarbonate, calcium carbonate, bismuth subsalicylate, or others; Maalox, Mylanta, Gaviscon, Kaopectate, Pepto-Bismol) sucralfate, esomeprazole, omeprazole, lansoprazole, dexlansoprazole, esomeprazole, pantoprazole, rabeprazole, ilaprazole, cimetidine, ranitidine, famotidine, lafutidine, nizatidine, roxatidine, tiotidine, salmeterol, albuterol, aclidinium, ipratropium, tiotropium, umeclidinium, acrivastine, azelastine, bilastine, brompheniramine, buclizine, bromodiphenhydramine, carbinoxamine, chlorpromazine, cyclizine, chlorphenamine, chlorodiphenhydramine, clemastine, cyproheptadine, dexbrompheniramine, dexchlorpheniramine, dimenhydrinate, dimetindene, diphenhydramine, doxylamine, ebastine, embramine, fexofenadine, hydroxyzine, loratadine, meclozine, mirtazapine, olopatadine, orphenadrine, phenindamine pheniramine, phenyltoloxamine, promethazine, quetiapine, rupatadine, tripelennamine, triprolidine, clobenpropit, ciproxifan, conessine, thioperamide, montelukast, zafirlukast, pranlukast, mepolizumab, reslizumab, omalizumab, infliximab, azathioprine, 6-mercaptopurine, thioguanine, aspirin (acetylsalicylic acid), ibuprofen, naproxen, ketoprofen, celecoxib, diclofenac, amikacin, gentamicin, kanamycin, neomycin, netilmicin, tobramycin, paromomycin, streptomycin, spectinomycin, geldanamycin, herbimycin, rifaximin, loracarbef, ertapenem, doripenem, imipenem/cilastatin, meropenem, cefadroxil, cefazolin, cefalotin, cefalexin, cefaclor, cefamandole, cefoxitin, cefprozil, cefuroxime, cefixime, cefdinir, cefditoren, cefoperazone, cefotaxime, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, cefepime, ceftaroline fosamil, ceftobiprole, teicoplanin, vancomycin, telavancin, dalbavancin, oritavancin, clindamycin, lincomycin, daptomycin, azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, troleandomycin, telithromycin, spiramycin, aztreonam, furazolidone, nitrofurantoin, linezolid, posizolid, radezolid, torezolid, amoxicillin, ampicillin, azlocillin, carbenicillin, cloxacillin, dicloxacillin, flucloxacillin, mezlocillin, methicillin, nafcillin, oxacillin, penicillin G, penicillin V, piperacillin, temocillin, ticarcillin, amoxicillin/clavulanate, ampicillin/sulbactam, piperacillin/tazobactam, ticarcillin/clavulanate, bacitracin, colistin, polymyxin B, ciprofloxacin, enoxacin, gatifloxacin, gemifloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, trovafloxacin, grepafloxacin, sparfloxacin, temafloxacin, mafenide, sulfacetamide, sulfadiazine, silver sulfadiazine, sulfadimethoxine, sulfamethizole, sulfamethoxazole, solfanilamide, sulfasalazine, sulfisoxazole, trimethoprim-sulfamethoxazole, sulfamidochrysoidine, demeclocycline, doxycycline, minocycline, oxytetracycline, tetracycline, clofazimine, dapsone, capreomycin, cycloserine, ethambutol, ethionamide, isoniazid, pyrazinamide, rifampicin, rifabutin, rifapentine, streptomycin, arsphenamine, chloramphenicol, fosfomycin, fusidic acid, metronidazole, mupirocin, platensimycin, quinupristin/dalfopristin, thiamphenicol, tigecycline, tinidazole, trimethoprim, or combinations thereof. 19. The pharmaceutical composition of claim 9, wherein the composition is useful for treating a subject suffering from one or more of oral or esophageal inflammation, eosinophilic esophagitis, inflammatory bowel disease involving the esophagus, oral lichen planus, aphthous stomatitis, Crohn's disease, esophageal inflammation secondary to caustic/irritant ingestion, recurrent esophageal strictures of any cause and including irritant ingestion, pill-induced esophagitis, systemic diseases, congential diseases, epidermolysis bullosa, trauma, or post-surgery inflammation odynophagia, acid reflux, dysphagia, oral, esophageal or peptic ulcers, heart burn, chest pain, abdominal pain, nausea, vomiting, coughing, sore throat, decrease in appetite. 20. A method for treating, retarding the progression of, prophylaxis of, delaying the onset of, ameliorating, or reducing the symptoms of one or more of esophageal, oral, or buccal inflammation, eosinophilic esophagitis, oral lichen planus, aphthous stomatitis, odynophagia, acid reflux, dysphagia, oral, esophageal or peptic ulcers, heart burn, chest pain, abdominal pain, nausea, vomiting, coughing, sore throat, decrease in appetite, or failure to thrive, comprising administering to a subject in need thereof the pharmaceutical composition of claim 9.

Details for Patent 10,195,211

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	August 24, 1998		2035-06-15
Genentech, Inc.	XOLAIR	omalizumab	For Injection	103976	June 20, 2003		2035-06-15
Genentech, Inc.	XOLAIR	omalizumab	Injection	103976	September 28, 2018		2035-06-15
Genentech, Inc.	XOLAIR	omalizumab	Injection	103976	August 17, 2023		2035-06-15
Glaxosmithkline Llc	NUCALA	mepolizumab	For Injection	125526	November 04, 2015		2035-06-15