Lyophilized pharmaceutical compositions
AssigneeAstex Pharmaceuticals, Inc.
InventorsRajashree JOSHI-HANGAL, Sanjeev REDKAR
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Abstract
The invention provides a method of preparing a lyophilized pharmaceutical composition containing a compound described herein or a pharmaceutically-acceptable salt thereof. The process comprises dissolving the compound in a solvent comprising dimethylsulfoxide and optionally one or more co-solvents to form a solution, and then removing the solvent and any co-solvents by a freeze-drying process. Also provided by the invention are lyophilized pharmaceutical compositions and their use in medicine and in particular in the treatment of cancer.
Claims28
A method of preparing a lyophilized pharmaceutical composition, the method comprising dissolving a compound of formula (1):
- or a pharmaceutically-acceptable salt thereof, in a solvent comprising dimethylsulfoxide (DMSO) to form a solution, wherein the solvent is then removed by a freeze-drying process to give a lyophilized product, wherein the freeze-drying process comprises:
- (i) a first freezing stage in which the solution is frozen by reducing the temperature thereof to a temperature of no greater than about −20° C.;
- (ii) a first warming stage in which the temperature of the frozen solution is raised to a temperature in the range from about −15° C. to about 5° C., wherein the temperature in the range from about −15° C. to about 5° C. keeps the solution frozen;
- (iii) a second freezing stage in which the temperature of the solution is lowered to a temperature of no greater than about −20° C.;
- (iv) a primary drying stage, wherein the primary drying stage comprises a sublimation step in which the DMSO is removed by sublimation from the solution in its frozen state under reduced pressure to give a partially dried product;
- and
- (v) a secondary drying stage in which the DMSO is removed by evaporation from the partially dried product in a non-frozen state under reduced pressure to give the lyophilized product.
A pharmaceutical composition prepared by a process comprising the steps of:
- dissolving a compound of formula (1):
- or a pharmaceutically-acceptable salt thereof, in a solvent comprising dimethylsulfoxide (DMSO) to form a solution, wherein the solvent is then removed by a freeze-drying process to give a lyophilized product, wherein the freeze-drying process comprises:
- (i) a first freezing stage in which the solution is frozen by reducing the temperature thereof to a temperature of no greater than about −20° C.;
- (ii) a first warming stage in which the temperature of the frozen solution is raised to a temperature in the range from about −15° C. to about 5° C., wherein the temperature in the range from about −15° C. to about 5° C. keeps the solution frozen;
- (iii) a second freezing stage in which the temperature of the solution is lowered to a temperature of no greater than about −20° C.;
- (iv) a primary drying stage, wherein the primary drying stage comprises a sublimation step in which the DMSO is removed by sublimation from the solution in its frozen state under reduced pressure to give a partially dried product;
- and
- (v) a secondary drying stage in which the DMSO is removed by evaporation from the partially dried product in a non-frozen state under reduced pressure to give the lyophilized product.
Dependencies are inferred from the claim text.