Liquisoft capsules

• US 9,867,779 B2
• Filed: 03/25/2016
• Issued: 01/16/2018
• Est. Priority Date: 03/26/2015
• Status: Active Grant

• Current Assignee: Patheon Softgels, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Patheon Softgels, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Zhao, Yinyan, Hu, Yunhua, Williams, Mervin, Dyakonov, Tatyana, Gosangari, Saujanya, Yang, Chue, Maria Van Duijnhoven, Henricus Marinus Gerardus, Piest, Martin, Fatmi, Aqeel A
• Primary Examiner(s): PURDY, KYLE A
• Application Number:
  US15/080,614
• Publication Number:
  US 20160279056A1
• Time in Patent Office: 662 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/045 Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/4825 Proteins, e.g. gelatin gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816
• CPC Class Codes: A61K 9/4833 Encapsulating processes; Filling of capsules mechanical aspects A61J3/07
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds

Abstract

Described herein are oral pharmaceutical compositions suitable for chewing, sucking, or buccal dissolution comprising soft gel capsules and liquid fills, methods for making the same, and methods for treating subjects in need thereof with such capsules. In particular, oral pharmaceutical compositions comprising chewable, suckable, or dissolvable soft gel capsules with various flowable fill compositions are described.

Claims

1. An oral pharmaceutical composition suitable for chewing, sucking, or buccal dissolution comprising a shell encapsulating a liquid matrix, wherein the shell comprises:

(a) about 20% by weight of the shell of gelatin having a bloom strength of 150;

(b) about 9% by weight of the shell of gelatin having a bloom strength of 100;

(c) about 5% by weight of the shell of hydrolyzed collagen;

(d) about 17% by weight of the shell of lycasin;

(e) about 25% by weight of the shell of glycerin;

(f) about 0.5% by weight of the shell of citric acid;

(g) about 2.5% about xylitol; and

(h) about 0.2% by weight of the shell of sucralose; and

the matrix comprises;

(i) about 21% by weight of the matrix of polyethylene glycol 400;

(j) about 8% by weight of the matrix of propylene glycol;

(k) about 1% by weight of the matrix of povidone K30;

(l) about 0.6% by weight of the matrix of sucralose;

(m) about 0.6% by weight of the matrix of acesulfame potassium;

(n) about 1% by weight of the matrix of citric acid;

(o) about 6% by weight of the matrix of water;

(p) about 1% by weight of the matrix of dextromethorphan hydrobromide; and

(q) about 0.1% by weight of the matrix of menthol.

2. A pharmaceutical combination comprising the composition of claim 1, and one or more additional therapeutic compounds.

3. The pharmaceutical combination of claim 2, wherein the one or more additional therapeutic compounds comprises one or more of NSAIDS, diphenhydramine, codeine, chlorhexidine, cimetidine, ranitidine, famotidine, ondansetron, omeprazole, lansoprazole, rabeprazole, esomeprazole, pantoprazole, calcium supplements, magnesium hydroxide, bupropion, or varenicline.

4. A method for treating for treating, retarding the progression of, prophylaxis of, delaying the onset of, ameliorating, reducing the symptoms of, or promoting health, including but not limited to of one or more of pain, inflammation, cough, cold, chest congestion, nasal congestion, sinusitis, throat or bronchial irritation, allergies, fever, flu, inflammation of the gastrointestinal tract, sour stomach, neoplasia, hyperthyroidism, hypercalcemia, hyperparathyroidism, parathyroid carcinoma, indigestion, heartburn, irritable bowels, constipation, diarrhea, insomnia, dry mouth, mouth odor, halitosis, stained teeth, oral pain, loss of enamel, nicotine desire;

cessation of urge to smoke, fatigue, or malaise comprising administering to a subject in need thereof the pharmaceutical combination of combination claim 2.

5. The composition of claim 1 wherein the dosage form is stable for at 25°

C. for at least one year.

6. A kit for dispensing the oral pharmaceutical composition of claim 1, the kit comprising:

(a) at least one oral pharmaceutical composition;

(b) at least one moisture proof dispensing receptacle comprising blister or strip packs, an aluminum blister, a transparent or opaque polymer blister with pouch, polypropylene tubes, colored blister materials, tubes, bottles, and bottles optionally containing a child-resistant feature, optionally comprising a desiccant, such as a molecular sieve or silica gel; and

optionally (c) at least one daily regimen for the oral pharmaceutical composition; and

(d) an insert comprising instructions or prescribing information for the oral pharmaceutical composition.

7. The kit of claim 6, that is useful for treating pain, inflammation, cough, cold, chest congestion, nasal congestion, sinusitis, throat or bronchial irritation, allergies, fever, flu, inflammation of the gastrointestinal tract, sour stomach, neoplasia, hyperthyroidism, hypercalcemia, hyperparathyroidism, parathyroid carcinoma, indigestion, heartburn, irritable bowels, constipation, diarrhea, insomnia, dry mouth, mouth odor, halitosis, stained teeth, oral pain, loss of enamel, nicotine desire, cessation of urge to smoke, fatigue, or malaise.

8. A method for manufacturing the oral pharmaceutical composition of claim 1 comprising the steps of:

(a) preparing a shell composition comprising gelatin, hydrolyzed collagen, glycerin, lycasin, citric acid, xylitol, and sucralose;

(b) mixing the shell composition under vacuum for 1 to 2 hours at a temperature of at least about 50°

C.;

(c) preparing a matrix fill composition comprising combining polyethylene glycol 400, propylene glycol, povidone K30, sucralose, acesulfame potassium, citric acid, water, dextromethorphan hydrobromide; and

menthol;

(d) mixing the matrix fill composition second solution at a temperature of at least about 50°

C.;

(e) casting the shell composition of (b) into films or ribbons using heat-controlled drums or surfaces while incorporating the matrix fill composition of (d); and

(f) forming a soft dosage form comprising a liquid matrix fill using rotary die encapsulation technology.

9. An oral pharmaceutical composition comprising a soft dosage form comprising an active pharmaceutical ingredient in a liquid matrix produced by the method of claim 8.