Solid dosage form comprising solid dispersion and method for producing the same

• US 20080038339A1
• Filed: 08/01/2007
• Published: 02/14/2008
• Est. Priority Date: 08/08/2006
• Status: Active Grant

• Current Assignee: Shin-Etsu Chemical Company Limited
• Original Assignee: Shin-Etsu Chemical Company Limited
• Inventors: Umezawa, Hiroshi, Kusaki, Fumie, Nishiyama, Yuichi, Hoshino, Takafumi, Maruyama, Naosuke, Fukui, Ikuo
• Granted Patent: US 8,343,547 B2
• Time in Patent Office: Days
• US Class Current: 424/464
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Abstract

Provided are a solid dosage form comprising a solid dispersion that allows a drug in the preparation to be rapidly dissolved without compromising the solubility of the solid dispersion, and a method for producing the same. More specifically, provided is a solid dosage form comprising a solid dispersion, the dispersion comprising: a poorly soluble drug, a water-soluble polymer and a disintegrant, wherein the disintegrant is low-substituted hydroxypropylcellulose having an average particle size of 10 to 100 μm and a specific surface area measured by BET method of at least 1.0 m²/g. Moreover, provided is a method for producing a solid dosage form comprising a solid dispersion, the method comprising steps of: spraying a water-soluble polymer solution in which a poorly soluble drug has been dispersed or dissolved, on a powder of low-substituted hydroxypropylcellulose having an average particle size of 10 to 100 μm and a specific surface area measured by BET method of at least 1.0 m²/g and serving as a disintegrant and granulating the resultant; and drying.

Claims

1. A solid dosage form comprising a solid dispersion, the dispersion comprising a poorly soluble drug, a water-soluble polymer and a disintegrant, wherein the disintegrant is low-substituted hydroxypropylcellulose having an average particle size of 10 to 100 μ

m and a specific surface area measured by BET method of at least 1.0 m²/g.

2. The solid dosage form comprising the solid dispersion according to claim 1, wherein said solid dispersion further comprises an excipient.

3. The solid dosage form comprising the solid dispersion according to claim 1, wherein said disintegrant is low-substituted hydroxypropylcellulose having 5 to 16% by weight of hydroxypropoxyl groups.

4. The solid dosage form comprising the solid dispersion according to claim 1, wherein said disintegrant is low-substituted hydroxypropylcellulose having a bulk density of at least 0.30 g/ml.

5. The solid dosage form comprising the solid dispersion according to claim 1, wherein said disintegrant is low-substituted hydroxypropylcellulose having an elastic recovery ratio of not greater than 7% when compression at a compression force of 50 MPa.

6. The solid dosage form comprising the solid dispersion according to claim 1, wherein said disintegrant is low-substituted hydroxypropylcellulose having a swollen volume increase ratio of at least 300% and a swollen volume increase rate of at least 100%/min when absorbing water.

7. The solid dosage form comprising the solid dispersion according to claim 1, wherein said disintegrant is low-substituted hydroxypropylcellulose having a repose angle of not greater than 42°

.

8. The solid dosage form comprising the solid dispersion according to claim 1, wherein said water-soluble polymer is selected from the group consisting of alkylcellulose, hydroxyalkylcellulose, hydroxyalkylalkylcellulose, polyvinyl alcohol, and polyvinyl pyrrolidone.

10. The solid dosage form comprising the solid dispersion according to claim 2, wherein said disintegrant is low-substituted hydroxypropylcellulose having 5 to 16% by weight of hydroxypropoxyl groups.

11. The solid dosage form comprising the solid dispersion according to claim 2, wherein said disintegrant is low-substituted hydroxypropylcellulose having a bulk density of at least 0.30 g/ml.

12. The solid dosage form comprising the solid dispersion according to claim 2, wherein said disintegrant is low-substituted hydroxypropylcellulose having an elastic recovery ratio of not greater than 7% when compression at a compression force of 50 MPa.

13. The solid dosage form comprising the solid dispersion according to claim 2, wherein said disintegrant is low-substituted hydroxypropylcellulose having a swollen volume increase ratio of at least 300% and a swollen volume increase rate of at least 100%/min when absorbing water.

14. The solid dosage form comprising the solid dispersion according to claim 2, wherein said disintegrant is low-substituted hydroxypropylcellulose having a repose angle of not greater than 42°

.

15. The solid dosage form comprising the solid dispersion according to claim 2, wherein said water-soluble polymer is selected from the group consisting of alkylcellulose, hydroxyalkylcellulose, hydroxyalkylalkylcellulose, polyvinyl alcohol, and polyvinyl pyrrolidone.

9. A method for producing a solid dosage form comprising a solid dispersion, the method comprising steps of:

spraying a water-soluble polymer solution in which a poorly soluble drug has been dispersed or dissolved, on a powder of low-substituted hydroxypropylcellulose having an average particle size of 10 to 100 μ

m and a specific surface area measured by BET method of at least 1.0 m²/g and serving as a disintegrant;

granulating the resultant; and

drying.