Controlled release and taste masking oral pharmaceutical composition

• US 10,154,964 B2
• Filed: 07/13/2018
• Issued: 12/18/2018
• Est. Priority Date: 09/07/2011
• 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:
  US16/034,664
• Publication Number:
  US 20180318225A1
• Time in Patent Office: 158 Days
• Field of Search: None
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/18 Sulfonamides compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/205 Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
• CPC Class Codes: A61K 31/221 with compounds having an amino group, e.g. acetylcholine, acetylcarnitine
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/606 having amino groups
• 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 9/2806 : 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

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. A tablet for the treatment of ulcerative colitis consisting essentially of (1) a tableted core, and (2) a coating on said tableted core, wherein said tableted core consists of a matrix comprising:

(a) 9 mg of budesonide;

(b) hydroxypropyl methylcellulose; and

(c) magnesium stearate;

wherein said coating on said tableted core comprises methacrylic acid copolymer type A, methacrylic acid copolymer type B, or a mixture of methacrylic acid copolymer type A and methacrylic acid copolymer type B;

wherein following oral administration of the tablet to a human, the tablet provides an AUC of said budesonide in said human of about 16.43±

10.52 (ng)×

(h)/mL;

and wherein said tablet provides extended release of budesonide in the colon of said human effective to treat ulcerative colitis in said human.

2. The tablet of claim 1, wherein said matrix further comprises hydroxypropyl cellulose, silicon dioxide, lactose, microcrystalline cellulose, and lecithin.

3. The tablet of claim 1, wherein said matrix further comprises starch or a starch derivative.

4. The tablet of claim 2, wherein said matrix further comprises starch or a starch derivative.

5. The tablet of claim 1, wherein said matrix does not comprise stearic acid.

6. The tablet of claim 2, wherein said matrix does not comprise stearic acid.

7. The tablet of claim 3, wherein said matrix does not comprise stearic acid.

8. The tablet of claim 4, wherein said matrix does not comprise stearic acid.

9. The tablet of claim 1, wherein said coating on said tableted core comprises a mixture of methacrylic acid copolymer type A and methacrylic acid copolymer type B.

10. The tablet of claim 8, wherein said coating on said tableted core comprises a mixture of methacrylic acid copolymer type A and methacrylic acid copolymer type B.

11. The tablet of claim 9, wherein the weight to weight ratio of said methacrylic acid copolymer type A to said methacrylic acid copolymer type B in said coating on said tableted core is from 1:

5 to 5;

1.

12. The tablet of claim 11, wherein the weight to weight ratio of said methacrylic acid copolymer type A to said methacrylic acid copolymer type B in said coating on said tableted core is about 1:

1.

13. The tablet of claim 10, wherein the weight to weight ratio of said methacrylic acid copolymer type A to said methacrylic acid copolymer type B in said coating on said tableted core is from 1:

5 to 5;

1.

14. The tablet of claim 13, wherein the weight to weight ratio of said methacrylic acid copolymer type A to said methacrylic acid copolymer type B in said coating on said tableted core is about 1:

1.

15. The tablet of claim 1, wherein said coating on said tableted core further comprises triethylcitrate.

16. The tablet of claim 1, wherein following oral administration of the tablet to a human, the tablet provides a C_max of said budesonide in said human of about 1.35±

0.96 ng/mL.

17. The tablet of claim 7, wherein following oral administration of the tablet to a human, the tablet provides a C_max of said budesonide in said human of about 1.35±

0.96 ng/mL.

18. The tablet of claim 5, wherein following oral administration of the tablet to a human, the tablet provides a C_max of said budesonide in said human of about 1.35±

0.96 ng/mL.

19. The tablet of claim 14, wherein following oral administration of the tablet to a human, the tablet provides a C_max of said budesonide in said human of about 1.35±

0.96 ng/mL.

20. The tablet of claim 1, wherein following oral administration of the tablet to a human, the tablet provides a T_max of said budesonide in said human of about 13.3±

5.9 hours.

21. The tablet of claim 7, wherein following oral administration of the tablet to a human, the tablet provides a T_max of said budesonide in said human of about 13.3±

5.9 hours.

22. The tablet of claim 5, wherein following oral administration of the tablet to a human, the tablet provides a T_max of said budesonide in said human of about 13.3±

5.9 hours.

23. The tablet of claim 8, wherein following oral administration of the tablet to a human, the tablet provides a T_max of said budesonide in said human of about 13.3±

5.9 hours.

24. The tablet of claim 14, wherein following oral administration of the tablet to a human, the tablet provides a T_max of said budesonide in said human of about 13.3±

5.9 hours.

25. The tablet of claim 16, wherein following oral administration of the tablet to a human, the tablet provides a T_max of said budesonide in said human of about 13.3±

5.9 hours.

26. A tablet consisting essentially of (1) a tableted core, and (2) a gastro-resistant coating on said tableted core, wherein said tableted core consists of a matrix comprising:

(a) 9 mg of budesonide;

(b) hydroxypropyl methylcellulose;

(c) magnesium stearate;

(d) hydroxypropyl cellulose;

(e) silicon dioxide;

(f) lactose;

(g) starch or a starch derivative;

(h) microcrystalline cellulose; and

(i) lecithin;

wherein said gastro-resistant coating comprises methacrylic acid copolymer type A, methacrylic acid copolymer type B and triethylcitrate;

wherein following oral administration of the tablet to a human, the tablet provides an AUC of said budesonide in said human of about 16.43±

10.52 (ng)×

(h)/mL;

and wherein said tablet provides extended release of budesonide in the colon of said human effective to treat ulcerative colitis in said human.

27. The tablet of claim 26, wherein following oral administration of the tablet to a human, the tablet provides a C_max of said budesonide in said human of about 1.35±

0.96 ng/mL.

28. The tablet of claim 26, wherein following oral administration of the tablet to a human, the tablet provides a T_max of said budesonide in said human of about 13.3±

5.9 hours.

29. A tablet consisting essentially of (1) a tableted core, and (2) a gastro-resistant coating 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;

wherein said coating on said tableted core comprises methacrylic acid copolymer type A, methacrylic acid copolymer type B, or a mixture of methacrylic acid copolymer type A and methacrylic acid copolymer type B;

wherein following oral administration of the tablet to a human, the tablet provides an AUC of said budesonide in said human of about 16.43±

10.52 (ng)×

(h)/mL, a C_max of said budesonide in said human of about 1.35±

0.96 ng/mL, and a T_max of said budesonide in said human of about 13.3±

5.9 hour,

and wherein said tablet provides extended release of budesonide in the colon of said human effective to treat ulcerative colitis in said human.

30. The tablet of claim 29, wherein said matrix further comprises starch or a starch derivative.