Hydrogel-driven drug dosage form

• US 20040052845A1
• Filed: 08/07/2003
• Published: 03/18/2004
• Est. Priority Date: 08/09/2000
• Status: Abandoned Application

• Current Assignee: Bend Research Inc. (Lonza Group AG)
• Original Assignee: Bend Research Inc. (Lonza Group AG)
• Inventors: Herbig, Scott M, Friesen, Dwayne T, Babcock, Walter C, Curatolo, William J, Beyerinck, Ronald A, Thombre, Avinash G, Chidlaw, Mark B, Appel, Leah E
• Application Number:
  US10/344,171
• Publication Number:
  US 20040052845A1
• Time in Patent Office: Days
• US Class Current: 424/471
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer

Abstract

A controlled release dosage form has a coated core with the core comprising a drug-containing composition and a water-swellable composition, each occupying separate regions within the core. The coating around the core is water-permeable, water-insoluble and has at least one delivery port therethrough. A variety of geometric arrangements are disclosed.

Claims

1. A controlled release drug dosage form comprising a core and a coating around said core wherein:

(a) said core comprises a drug-containing composition, another drug-containing composition, and a water-swellable composition, each occupying separate regions within said core, said water-swellable composition being located between said drug-containing composition and said another drug-containing composition; and

(b) said coating is water-permeable, water-insoluble, and has at least one delivery port for communication with said drug-containing composition and another delivery port for communication with said another drug-containing composition.

5. The dosage form of claim 1 wherein said drug-containing composition has a different formulation than said another drug-containing composition.

6. The dosage form of claim 1 wherein said drug-containing composition comprises a low-solubility drug, and said first drug-containing composition comprises a drug-entraining agent.

8. The dosage form of any one of claims 1-3 wherein said drug-containing composition further comprises a swelling agent.

9. The dosage form of any one of claims 1-4 wherein said core further comprises a solubilizing agent.

10. The dosage form of any one of claims 1-3 wherein said drug-containing composition further comprises a fluidizing agent having a solubility of at least 30 mg/mL and said fluidizing agent comprises at least 10 wt of said drug-containing composition, and said fluidizing agent is selected from the group consisting of an organic acid, a salt, a sugar, an amino acid, a polyol, and a low-molecular weight oligomer of a water-soluble polymer.

11. The dosage form of any one of claims 14 comprising an ionic swelling agent.

12. The dosage form of any one of claims 1-3 wherein said water-swellable composition has a swelling ratio of at least 2.

14. The dosage form of any one of claims 1-4 wherein said coating has a water flux (40/75) of at least 1.0×

10<sup>−

3</sup> gm/cm²−

hr.

15. The dosage form of any one of claims 14 and 14 wherein said coating has a durability of at least 1 Kp/cm².

16. The dosage form of any one of claims 1-4 wherein said coating is formed from a solution having a weight ratio of cellulose acetate to polyethylene glycol of from 9:

1 to 6.5;

3.5.

17. The dosage form of any one of claims 14 wherein said coating comprises a polymeric asymmetric membrane comprising a thick, porous region and a dense thin region.

20. The dosage form of any one of claims 1-4 wherein said core further comprises a concentration-enhancing polymer.

2. A controlled release drug dosage form comprising a core and a coating around said core wherein:

(a) said core comprises a drug-containing composition and a water-swellable composition, each occupying separate regions within said core, said drug-containing composition surrounding said water-swellable composition;

(b) said drug-containing composition comprises a low-solubility drug and a drug-entraining agent;

(c) said water-swellable composition comprises a swelling agent; and

(d) said coating is water-permeable, water-insoluble, and has at least one delivery port therethrough.

7. The dosage form of any one of claims 2-4 and 6 wherein said drug-entraining agent is selected from the group consisting of polyols, oligomers of polyethers, mixtures of polyfunctional organic acids, cationic materials, polyethylene oxide, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, methyl cellulose, carboxyethylcellulose, gelatin, and xanthan gum.

13. The dosage form of any one of claims 2-4 and 6 wherein said low-solubility drug is selected from the group consisting of sildenafil and pharmaceutically acceptable salts of sildenafil, sertraline and pharmaceutically acceptable salts of sertraline, the mesylate salt of the drug 4-[3-[4-(2-methylimidazol-1-yl) phenylthio]phenyl]-3,4,5,6-tetrahydro-2H-pyran-4-carboxamide hemifumarate, nifedipine, (+)-2-(3-benzyl-4hydroxy-chroman-7-yl)-4-trifluoromethyl-benzoic acid, 4-amino-5-(4-fluorophenyl)-6,7-dimethoxy-2-[4-(morpholinocarbonyl) perhydro-1,4-diazepin-1-yl]quinoline, and 5-(2-(4-(3-benzisothiazolyl)-piperazinyl)ethyl-6-chlorooxindole.

18. The dosage form of any one of claims 2-4 and 6 wherein, following introduction of said dosage form to a use environment, no more than 50 wt % of said low-solubility drug is released to said use environment within 2 hours and at least 60 wt % to said use environment is released within 12 hours.

19. The dosage form of any one of claims 2-4 and 6 wherein, following introduction of said dosage form to a use environment, at least about 80 wt %/o of said low-solubility drug is released to said use environment within about 24 hours.

3. A controlled release drug dosage form comprising a core and a coating around said core wherein:

(a) said core comprises a drug-containing composition and a water-swellable composition, each occupying separate regions within said core, said water-swellable composition comprising a plurality of granules;

(b) said drug-containing composition comprises a low-solubility drug and a drug-entraining agent;

(c) said water-swellable-composition comprises a swelling agent; and

(d) said coating is water-permeable, water-insoluble, and has at least one delivery port therethrough.

4. A controlled release drug dosage form comprising a core and a coating around said core wherein:

(a) said core is substantially homogeneous throughout and comprises a mixture of a low-solubility drug, a drug-entraining agent, and a swelling agent; and

(b) said coating is water-permeable, water-insoluble, and has at least one delivery port therethrough.