Drying of Drug-Containing Particles

• US 20080213375A1
• Filed: 01/16/2006
• Published: 09/04/2008
• Est. Priority Date: 01/28/2005
• Status: Active Grant

• Current Assignee: Lonza Bend Incorporated (Lonza Group AG)
• Original Assignee: Pfizer Inc.
• Inventors: Dobry, Daniel Elmont, Beyerinck, Ronald Arthur, Ray, Roderick Jack, Dixon, David, Grove, Kevin Douglas
• Granted Patent: US 9,265,731 B2
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A secondary drying process is disclosed for removing residual solvent from drug-containing particles that have been formed by solvent-based processes, the secondary drying process utilizing a combination of vacuum, agitation, and a stripping gas.

Claims

1. A process for producing a pharmaceutical composition, the process comprising:

(a) forming a solution comprising a drug, an excipient and a solvent;

(b) atomizing said solution into droplets and removing at least a portion of said solvent from said droplets so as to form at least partially non-crystalline drug-containing particles, wherein said drug-containing particles contain less than about 10 wt % of said solvent; and

(c) drying said drug-containing particles by

(i) introducing said drug-containing particles into a drying chamber having an external wall;

(ii) circulating said drug-containing particles within said drying chamber by means of a mechanical agitator independent of said wall;

(iii) flowing a stripping gas through said drying chamber; and

(iv) removing said stripping gas and at least a portion of said solvent from said drying chamber.

3. The process of claim 1 wherein said step (ii) of circulating said particles further comprises flowing said stripping gas through a bed of said particles.

5. The process of any one of claims 1 and 2 wherein said particles in said drying chamber are in a bed having an average depth of at least 10 cm.

6. The process of any one of claims 1 and 2 wherein said excipient is a polymer.

7. The process of claim 6 wherein said drug-containing particles are in the form of a solid amorphous dispersion.

8. The process of any one of claims 1 and 2 wherein said particles have a bulk specific volume of at least about 1.5 mL/g, and an mean diameter of less than about 500 μ

m.

9. The process of any one of claims 1 and 2 wherein the amount of solvent remaining in said particles after said process is less than about 0.5 wt % of the total mass of said particles.

10. The process of any one of claims 1 and 2 wherein the amount of solvent removed from said particles is at least about 90 wt % of the solvent originally present in said particles.

11. The process of any one of claims 1 and 2 wherein said total pressure in said drying chamber is less than about 0.1 atm.

12. The process of any one of claims 1 and 2 wherein said stripping gas has a flow rate of at least about 0.2 standard liters per minute per kilogram of particles to be dried.

13. The process of any one of claims 1 and 2 wherein said drug is a cholesteryl ester transfer protein inhibitor selected from the group consisting of [2R,4S]-4-[acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester, [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, (2R)-3-[[3-(4-chloro-3-ethylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol, and (2R,4R,4aS)-4-[amino-(3,5-bis-(trifluoromethyl-phenyl)-methyl]-2-ethyl-6-(trifluoromethyl)-3,4-dihydroquinoline-1-carboxylic acid isopropyl ester, S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate.

14. The process of claim 13 wherein said cholesteryl ester transfer protein inhibitor is torcetrapib, having the structure:

15. The product of the process of any one of claims 1 to 4.

2. A process for producing a pharmaceutical composition, the process comprising:

(a) forming a solution comprising a drug, an excipient and a solvent;

(b) atomizing said solution into droplets and removing at least a portion of said solvent from said droplets so as to form at least partially non-crystalline drug-containing particles, wherein said drug-containing particles contain less than about 10 wt % of said solvent; and

(c) drying said drug-containing particles by

(i) introducing said drug-containing particles into a drying chamber having an external wall;

(ii) circulating said drug-containing particles within said drying chamber;

(iii) flowing a stripping gas through said drying chamber and simultaneously maintaining a total pressure within said drying chamber that is less than about 0.75 atm; and

(iv) removing said stripping gas and at least a portion of said solvent from said drying chamber

wherein said step (ii) of circulating said particles comprises flowing said stripping gas through a bed of said particles.

4. The process of claim 2 wherein said step (ii) further comprises a mechanical agitator to circulate said particles.