Drying of drug-containing particles

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

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

(b) in a spray drying apparatus, atomizing said solution into droplets and removing at least a portion of said solvent from said droplets so as to form at least partially noncrystalline drug-containing particles containing less than about 10 wt % of said solvent; and

(c) conducting a secondary drying of said drug-containing particles of step (b) by

(i) removing the drug-containing particles from the spray drying apparatus and introducing said drug-containing particles of step (b) into a secondary drying apparatus having an external wall, the secondary drying apparatus being a separate chamber from the spray drying apparatus;

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

(iii) flowing a stripping gas through said secondary drying apparatus while reducing a total pressure to and maintaining the total pressure, within said secondary drying apparatus at less than about 0.75 atm;

(iv) conducting the secondary drying step for about 30 minutes to about 20 hours to remove solvent from the drug-containing particles such that the drug-containing particles contain less than about 0.5 wt % of the solvent; and

(v) removing said stripping gas and at least a portion of said solvent from said secondary drying apparatus.

2. The process of claim 1 wherein step (c)(iii) further comprises forming a bed of said drug-containing particles and flowing said stripping gas through said bed.

3. The process of claim 2 wherein said drug-containing particles in said secondary drying apparatus are in a bed having an average depth of at least 10 cm.

4. The process of claim 1 wherein the secondary drying step is conducted for about 30 minutes to about 2 hours.

5. The process of claim 4 wherein said drug-containing particles are in the form of a solid amorphous dispersion.

6. The process of claim 1 wherein the amount of solvent remaining in said drug-containing particles after said process is less than about 0.1 wt % of the total mass of said particles.

7. The process of claim 1 wherein the secondary drying step is conducted for about 30 minutes to about 4 hours.

8. The process of claim 1 wherein said total pressure in said secondary drying apparatus is less than about 0.1 atm.

9. The process of claim 1 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.

10. The process of claim 1 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-3,4dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, [2R,4S]4-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonylamino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester, [2R,4S]4-[(3,5-bistrifluoromethylbenzyl)-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.