Controlled release and taste masking oral pharmaceutical compositions

• US 10,064,878 B2
• Filed: 12/05/2016
• Issued: 09/04/2018
• Est. Priority Date: 06/14/1999
• Status: Expired due to Fees

• Current Assignee: Cosmo Technologies Limited (Cosmo Pharmaceuticals NV)
• Original Assignee: Cosmo Technologies Limited (Cosmo Pharmaceuticals NV)
• Inventors: Villa, Roberto, Pedrani, Massimo, Ajani, Mauro, Fossati, Lorenzo
• Primary Examiner(s): Tran, Susan T
• Application Number:
  US15/369,296
• Publication Number:
  US 20170143741A1
• Time in Patent Office: 638 Days
• Field of Search: None
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/28 Dragees; Coated pills or tablets , e.g. with film or compression coating A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209
• CPC Class Codes: A61K 9/2806 Coating materials
• CPC Class Codes: A61K 9/2813 Inorganic compounds
• CPC Class Codes: A61K 9/282 Organic compounds, e.g. fats
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 11/14 : Antitussive agents
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 : Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 : Anxiolytics
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/12 : Antihypertensives

Abstract

The invention relates to tablet comprising granules dispersed in at least one hydrophilic compound or matrix. The granules contain an active agent, at least one amphiphilic compound and at least one lipophilic compound. The tablet may include a gastro-resistant film coating.

Claims

1. A controlled release oral pharmaceutical composition in the form of a tablet comprising:

(1) a tablet core comprising a mixture of;

(i) budesonide in an amount effective to treat intestinal inflammatory disease; and

(ii) a macroscopically homogenous structure comprising;

(a) at least one lipophilic compound; and

(b) at least one hydrophilic compound; and

(2) a gastro-resistant coating applied directly to the tablet core that prevents release of budesonide in the stomach,

wherein the budesonide is dispersed in the macroscopically homogenous structure and wherein the macroscopically homogenous structure controls the release kinetics of the budesonide from the tablet in the gastrointestinal tract.

2. The controlled release oral pharmaceutical composition according to claim 1, wherein the gastro-resistant coating comprises at least one compound selected from the group consisting of methacrylic acid polymers and cellulose derivatives.

3. The controlled release oral pharmaceutical composition according to claim 2, wherein the gastro-resistant film comprises at least one methacrylic acid polymer.

4. The controlled release oral pharmaceutical composition according to claim 1, wherein the at least one lipophilic compound comprises a compound selected from the group consisting of an unsaturated or hydrogenated alcohol or fatty acid, salt, ester, or amide thereof, a fatty acids mono-, di- or triglyceride, or a polyethoxylated derivative thereof, a wax, ceramide, and a cholesterol derivative.

5. The controlled release oral pharmaceutical composition according to claim 4 wherein the at least one lipophilic compound comprises stearic acid or magnesium stearate.

6. The controlled release oral pharmaceutical composition according to claim 5 wherein the at least one lipophilic compound comprises stearic acid.

7. The controlled release oral pharmaceutical composition according to claim 1, wherein the at least one hydrophilic compound comprises a compound selected from the group consisting of an acrylic or methacrylic acid polymer or copolymer, an alkylvinyl polymer, a hydroxyalkyl cellulose, a carboxyalkyl cellulose, a polysaccharide, dextrin, pectin, starch, a natural or synthetic gum, and alginic acid.

8. The controlled release oral pharmaceutical composition according to claim 7, wherein the at least one hydrophilic compound comprises a hydroxyalkyl cellulose or a carboxyalkyl cellulose.

9. The controlled release oral pharmaceutical composition according to claim 8, wherein the at least one hydrophilic compound comprises a hydroxyalkyl cellulose.

10. The controlled release oral composition according to claim 1, wherein the macroscopically homogeneous structure further comprises at least one amphiphilic compound.

11. The controlled release oral pharmaceutical composition according to claim 10, wherein the at least one amphiphilic compound comprises a compound selected from the group consisting of lecithin, phosphatidylcholine, phosphatidylethanolamine, ceramide, and a glycol alkyl ether.

12. The controlled release oral pharmaceutical composition according to claim 11, wherein the at least one amphiphilic compound comprises lecithin.

13. The controlled release oral pharmaceutical composition according to claim 1, wherein the macroscopically homogeneous structure further comprises at least one compound selected from the group consisting of a chitosan, a polyacrylamide, a natural or synthetic gum, and an acrylic acid polymer.

14. The controlled release oral pharmaceutical composition according to claim 1, wherein the macroscopically homogenous structure further comprises microcrystalline cellulose.

15. A method for treating intestinal inflammatory disease comprising administering to a patient the controlled release oral pharmaceutical composition according to claim 1.

16. A controlled release oral pharmaceutical composition in the form of a tablet comprising:

(1) a tablet core comprising a mixture of;

(i) 9 mg budesonide; and

(ii) a macroscopically homogenous structure comprising;

(a) stearic acid;

(b) lecithin;

(c) hydroxypropyl cellulose; and

(2) a gastro-resistant coating, comprising at least one methacrylic acid polymer, applied directly to the tablet core that prevents release of budesonide in the stomach,

wherein the budesonide is dispersed in the macroscopically homogenous structure and wherein the macroscopically homogenous structure controls the release kinetics of the budesonide from the tablet in the gastrointestinal tract.

17. The controlled release oral pharmaceutical composition according to claim 16, wherein the macroscopically homogeneous structure further comprises microcrystalline cellulose, lactose monohydrate, silicon dioxide, and magnesium stearate.

18. The controlled release oral pharmaceutical composition according to claim 17, wherein the gastro-resistant coating further comprises talc, titanium dioxide, and triethylcitrate.

19. A method for treating intestinal inflammatory disease comprising administering to a patient the controlled release oral pharmaceutical composition according to claim 18.