Process for making compositions with poorly compressible therapeutic compounds

• US 20100152299A1
• Filed: 05/08/2006
• Published: 06/17/2010
• Est. Priority Date: 05/10/2005
• Status: Abandoned Application

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Tong, Wein-Qin, Lakshman, Jay, Serajuddin, Abu T., Kowalsi, James, Joshi, Yatindra, Vasanthavada, Madhav
• Application Number:
  US11/909,509
• Publication Number:
  US 20100152299A1
• Time in Patent Office: Days
• US Class Current: 514/632
• 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 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• 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: A61P 3/10 for hyperglycaemia, e.g. antidiabetics

Abstract

A process for preparing solid dosage forms that contain poorly compressible therapeutic compound. The process, for example, provides for the inventive use of an extruder, especially a twin screw extruder, to melt granulate a therapeutic compound(s) with a granulation excipient.

Claims

1. A process for making a pharmaceutical composition comprising the steps of:

combining a poorly compressible therapeutic compound with at least one granulating component to form a mixture;

kneading said mixture in an extruder while heating said mixture to a heating temperature less than a melting point of said therapeutic compound; and

extruding said mixture to form granules.

2. The process of claim 1, further comprising the step of compressing said granules to form a solid oral dosage form.

3. The process of claim 1, wherein said granulating component is a polymer having a Tg less than said melting point.

4. The process of claim 3, wherein said polymer is selected from the group consisting of water-soluble polymers, water-swellable polymers and water-insoluble polymers.

5. The process of claim 4, wherein said heating temperature is greater than or equal to said Tg.

6. The process of claim 3, wherein said mixture further comprises a plasticizer.

7. The process of claim 1, wherein said pharmaceutical composition is an immediate-release composition.

8. The process of claim 1, wherein said pharmaceutical composition is a sustained-release composition.

9. The process of claim 8, wherein said pharmaceutical composition comprises a release retardant.

10. The process of claim 1, wherein said extruding is through a die.

11. The process of claim 1, wherein said extruder is a twin-screw extruder.

14. Pharmaceutical granules prepared by the process of claim 1.

15. The pharmaceutical granules of claim 14, wherein said therapeutic compound is metformin hydrochloride.

17. The pharmaceutical granules of claim 15, wherein said metformin hydrochloride is present between 250 mg to 2000 mg.

18. A pharmaceutical composition comprising granules made by the process of claim 1, wherein said pharmaceutical composition has a hardness between 15 kP to 35 kP.

12. A process for making a pharmaceutical composition comprising the steps of:

combining a moisture sensitive therapeutic compound with at least one granulating component to form a mixture;

kneading said mixture in an extruder while heating said mixture to a heating temperature less than a melting point of said therapeutic compound; and

extruding said mixture to form granules.

13. A process for improving the friability of a tablet containing a poorly compressible therapeutic compound comprising the steps of:

combining a poorly compressible therapeutic compound with at least one granulating component to form a mixture;

kneading said mixture in an extruder while heating said mixture to a heating temperature less than a melting point of said therapeutic compound

extruding said mixture to form granules; and

compressing said granules into a tablet.

16. A pharmaceutical composition comprising pharmaceutical granules of claim 13 and an additional therapeutic compound.

19-21. -21. (canceled)