PROCESS FOR MAKING DRUG CRYSTALS OF DESIRED SIZE DISTRIBUTION AND MORPHOLOGY

1 . A process for providing crystals of fluticasone propionate of desired size distribution and morphology, the process comprising:

providing recrystallized columnar crystals of fluticasone propionate having aspect ratios of larger than 1 and less than 20, the aspect ratio of each recrystallized columnar crystal being the ratio of a longest dimension along a lengthwise axis relative to a shortest dimension of a transverse plane perpendicular to the lengthwise axis, wherein at least 90% by mass of the recrystallized columnar crystals have the shortest dimensions in the range of 50-250 microns; and

sizing the recrystallized columnar crystals to provide a collection of sized crystals having target dimensions, wherein, no more than 10% of the collection of the sized crystals by mass are less than 30 microns, wherein the sizing includes segmenting at least a portion of the recrystallized columnar crystals along the respective lengthwise axes while retaining the dimensions of the transverse plane perpendicular to the lengthwise axis.

2 . The process of claim 1 wherein the recrystallized columnar crystals further meet one or more of the following criteria:

(i) 90% of the recrystallized columnar crystals by mass are no larger than 1200 microns;

(ii) 50% of the recrystallized columnar crystals by mass are less than 350±180 microns; and

(iii) no more than 10% of the recrystallized columnar crystals by mass are less than 50 microns.

3 . The process of claim 1 wherein the recrystallized columnar crystals further meet one or more of the following criteria:

(i) 50% of the recrystallized columnar crystals by mass are in the range of 80 to 600 microns;

(ii) 75% of the recrystallized columnar crystals by mass are in the range of 50 to 800 microns; and

(iii) 90% of the recrystallized columnar crystals by mass are in the range of 20 to 1100 microns.

4 . The process of claim 1 wherein the collection of the sized crystals meet one or more of the following target dimensions:

(i) 90% of the sized crystals by mass are no larger than 190 microns;

(ii) 50% of the sized crystals by mass are less than 90±20 microns;

(iii) 75% or more of a total amount by volume of the sized crystals have an aspect ratio of 1-3.

5 . The process of claim 1 wherein the collection of the sized crystals meet one or more of the following target dimensions:

(i) 50% of the sized crystals by mass are in the range of 35 to 130 microns;

(ii) 75% of the sized crystals by mass are in the range of 30 to 145 microns; and

(iii) 90% of the sized crystals by mass are in the range of 25 to 170 microns.

6 . The process of claim 1 wherein the sizing comprises shortening the lengthwise axes of the recrystallized columnar crystals in a rotor/stator homogenizer to provide shortened crystals.

7 . The process of claim 6 wherein the sizing further comprising sieving the shortened crystals to provide sieved crystals.

8 . The process of claim 7 wherein the sieved crystals are rinsed one or more times with a rinsing liquid comprising a surfactant and one or more solvents selected from the group consisting of water, methanol, ethanol, and isopropanol.

9 . The process of claim 8 wherein the rinsing liquid comprises 0.05-1% (w/w) of polysorbate 80.

10 . The process of claim 1 wherein the sized crystals are further individually coated with a polymer membrane by a fluid bed coating equipment.

11 . The process of claim 10 wherein the polymer membrane is formed of polyvinyl alcohol, polylactic acid (PLA), polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL), poly(trimethylene carbonate) (pTMC) or a combination thereof.