Process for the preparation of fluticasone propionate form 1
AssigneePfizer Inc.
InventorsMartyn David Ticehurst, Ivan Marziano, Eleftherios Kougoulos
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Abstract
The invention relates to a novel crystallization process for preparing fluticasone propionate as crystalline form 1 polymorph with controlled particle size and suitable for micronization. Said process comprises the step of dissolving fluticasone propionate in acetone or in a mixture of acetone and water and then adding this solution to water or to a mixture of water 10 and acetone, thereby causing fluticasone propionate to crystallize out of the solution as crystalline form.
Claims19
A process for preparing fluticasone propionate as crystalline polymorphic Form 1 having a controlled particle size, comprising:
- dissolving fluticasone propionate in a first volume of a solvent to form a solution;
- then adding the entire solution to a vessel containing a second volume of a non-solvent, forming a solvent/non-solvent slurry, thereby causing fluticasone propionate to crystallise out of the solution as crystalline Form 1;
- and, after said adding the entire solution is completed, holding the slurry, with agitation, in said vessel;
- wherein the solvent comprises acetone and from 0% to 10% water, based on the volume of the solvent;
- wherein the non-solvent comprises water and from 0% to 25% acetone, based on the volume of the non-solvent;
- and wherein the process is a batch process, and the controlled particle size has a 10th percentile volume diameter D[v, 0.1] of between 1.3 microns and 3.4 microns;
- a 50th percentile volume diameter D[v, 0.5] of between 2.8 microns and 11.4 microns;
- and a 90th percentile volume diameter D [v, 0.9] of between 5.6 microns and 32.1 microns.
A process for preparing fluticasone propionate as crystalline polymorphic Form 1 having a controlled particle size, comprising:
- dissolving fluticasone propionate in a first volume of a solvent to form a solution;
- and then adding the entire solution to a vessel containing a second volume of a non-solvent, forming a solvent/non-solvent slurry, thereby causing fluticasone propionate to crystallise out of the solution as crystalline Form 1;
- wherein the solvent comprises acetone and from 0% to 10% water, based on the volume of the solvent;
- wherein the non-solvent comprises water and from 0% to 25% acetone, based on the volume of the non-solvent;
- wherein after the step of adding the entire solution to the non-solvent is completed, the solvent/non-solvent slurry is stirred in said vessel over a period of between about 1 and about 12 hours followed by filtration of the slurry to recover fluticasone propionate as crystalline Form 1 and drying of the recovered fluticasone propionate;
- and wherein the process is a batch process, and the controlled particle size has a 10th percentile volume diameter D[v, 0.1] of between 1.3 microns and 3.4 microns;
- a 50th percentile volume diameter D[v, 0.5] of between 2.8 microns and 11.4 microns;
- and a 90th percentile volume diameter D [v, 0.9] of between 5.6 microns and 32.1 microns.
A process for preparing fluticasone propionate as crystalline polymorphic Form 1 having a defined median particle size, comprising:
- dissolving fluticasone propionate in a first volume of a solvent ‘to form a solution;
- then adding the entire solution to a container of a second volume of a water-containing nonsolvent, thereby causing fluticasone propionate to crystallize out of the solution as crystalline Form 1 in a solvent/non-solvent slurry and, after the adding the entire solution is completed;
- stirring the solvent/non-solvent slurry in the container for a period of between about 1 and about 12 hours in the absence of ultrasound;
- and removing the solvent/non-solvent slurry from the container after the stirring and recovering fluticasone propionate Form 1 by filtration of the solvent/non-solvent slurry, wherein the solvent comprises acetone and from 0% to 10% water, based on the volume of the solvent;
- and wherein the non-solvent comprises water and from 0% to 25% acetone, based on the volume of the non-solvent;
- and, wherein the process is a batch process, and the controlled particle size has a 10th percentile volume diameter D[v, 0.1] of between 1.3 microns and 3.4 microns;
- a 50th percentile volume diameter D[v, 0.5] of between 2.8 microns and 11.4 microns;
- and a 90th percentile volume diameter D [v, 0.9] of between 5.6 microns and 32.1 microns.
Dependencies are inferred from the claim text.