Controlled release and taste masking oral pharmaceutical composition

• US 10,052,286 B2
• Filed: 07/11/2017
• Issued: 08/21/2018
• Est. Priority Date: 06/14/1999
• Status: Active Grant

• 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:
  US15/646,585
• Publication Number:
  US 20170304209A1
• Time in Patent Office: 406 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 9/2013 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 9/2045 Polyamides; Polyaminoacids, e.g. polylysine
• 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 9/2081 with microcapsules or coated microparticles according to A61K9/50
• 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 9/2813 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: H05K 999/99 dummy group

Abstract

Controlled release and taste masking compositions containing one or more active principles inglobated in a three-component matrix structure, i.e. a structure formed by successive amphiphilic, lipophilic or inert matrices and finally inglobated or dispersed in hydrophilic matrices. The use of a plurality of systems for the control of the dissolution of the active ingredient modulates the dissolution rate of the active ingredient in aqueous and/or biological fluids, thereby controlling the release kinetics in the gastrointestinal tract.

Claims

1. An oral dosage form consisting essentially of (1) a tableted core, and (2) a gastro-resistant film on said tableted core, wherein said tableted core consists of a matrix comprising:

(a) 9 mg of budesonide;

(b) hydroxypropyl cellulose; and

(c) magnesium stearate, stearic acid, or a mixture thereof;

and wherein following oral administration of the oral dosage form to a human, the oral dosage form provides an AUC_0-infinity of said budesonide in said human of about 16431.2±

10519.8 (pg)×

(h)/mL, wherein said oral dosage form is in the form of a tablet and provides extended release of budesonide in the colon of said human effective to treat ulcerative colitis in said human.

2. The oral dosage form of claim 1, wherein said matrix further comprises lecithin.

3. The oral dosage form of claim 1, wherein said matrix further comprises silicon dioxide.

4. The oral dosage form of claim 1, wherein said matrix comprises magnesium stearate and further comprises starch or a starch derivative.

5. The oral dosage form of claim 4, wherein said matrix comprises starch.

6. The oral dosage form of claim 4, wherein said matrix comprises a starch derivative.

7. The oral dosage form of claim 1, wherein said matrix comprises magnesium stearate, and further comprises lecithin, silicon dioxide, and starch or a starch derivative.

8. The oral dosage form of claim 1, wherein said gastro-resistant coating comprises acrylic acid polymer, methacrylic acid polymer, or a mixture thereof.

9. The oral dosage form of claim 4, wherein said wherein said gastro-resistant coating comprises acrylic acid polymer, methacrylic acid polymer, or a mixture thereof.

10. The oral dosage form of claim 7, wherein said wherein said gastro-resistant coating comprises acrylic acid polymer, methacrylic acid polymer, or a mixture thereof.

11. An oral dosage form consisting essentially of (1) a tableted core, and (2) a gastro-resistant film on said tableted core, wherein said tableted core consists of a matrix comprising:

(a) 9 mg of budesonide;

(b) hydroxypropyl cellulose; and

(c) magnesium stearate, stearic acid, or a mixture thereof;

and wherein following oral administration of the oral dosage form to a human, the oral dosage form provides a C_max of said budesonide in said human of about 1348.8±

958.8 pg/mL, wherein said oral dosage form is in the form of a tablet and provides extended release of budesonide in the colon of said human effective to treat ulcerative colitis in said human.

12. The oral dosage form of claim 11, wherein said matrix further comprises lecithin.

13. The oral dosage form of claim 11, wherein said matrix further comprises silicon dioxide.

14. The oral dosage form of claim 11, wherein said matrix comprises magnesium stearate and further comprises starch or starch derivative.

15. The oral dosage form of claim 14, wherein said matrix comprises starch.

16. The oral dosage form of claim 14, wherein said matrix comprises a starch derivative.

17. The oral dosage form of claim 11, wherein said matrix comprises magnesium stearate and further comprises lecithin, silicon dioxide, and starch or a starch derivative.

18. The oral dosage form of claim 11, wherein said gastro-resistant coating comprises acrylic acid polymer, methacrylic acid polymer, or a mixture thereof.

19. The oral dosage form of claim 14, wherein said wherein said gastro-resistant coating comprises acrylic acid polymer, methacrylic acid polymer, or a mixture thereof.

20. The oral dosage form of claim 17, wherein said wherein said gastro-resistant coating comprises acrylic acid polymer, methacrylic acid polymer, or a mixture thereof.

21. A method of treating a human subject with ulcerative colitis, comprising administering to said human subject an oral dosage form consisting essentially of

(1) a tableted core, and (2) a gastro-resistant film on said tableted core, wherein said tableted core consists of a matrix comprising:

(a) 9 mg of budesonide;

(b) hydroxypropyl cellulose; and

(c) magnesium stearate, stearic acid, or a mixture thereof;

and wherein following oral administration of the oral dosage form to a human, the oral dosage form provides an AUC_0-infinity, of said budesonide in said human of about 16431.2±

10519.8 (pg)×

(h)/mL, wherein said oral dosage form is in the form of a tablet and provides extended release of budesonide in the colon of said human effective to treat ulcerative colitis in said human.

22. A method of treating a human subject with ulcerative colitis, comprising administering to said human subject an oral dosage form consisting essentially of (1) a tableted core, and (2) a gastro-resistant film on said tableted core, wherein said tableted core consists of a matrix comprising:

(a) 9 mg of budesonide;

(b) hydroxypropyl cellulose; and

(c) magnesium stearate, stearic acid, or a mixture thereof;

and wherein following oral administration of the oral dosage form to a human, the oral dosage form provides a C_max of said budesonide in said human of about 1348.8±

958.8 pg/mL, wherein said oral dosage form is in the form of a tablet and provides extended release of budesonide in the colon of said human effective to treat ulcerative colitis in said human.