Crystalline l-arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta [b]indol-3-yl)acetic acid(compound1) for use in SIPI receptor-associated disorders

A method for preparing a crystalline free-plate habit of L-arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid that is substantially free of radial clusters or spherulites, said method comprising the steps of:

• a) forming a first mixture comprising L-arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid, a water-miscible anti-solvent, and H2O;
• b) heating the first mixture to a first heating temperature to form a second mixture;
• wherein said first heating temperature is about 79° C. to about 85° C.;
• c) adding a first additional amount of said water-miscible anti-solvent to said second mixture while maintaining said first heating temperature to form a suspension;
• d) cooling the suspension to a first cooling temperature and thereafter heating to a second heating temperature;
• wherein said first cooling temperature is about 18° C. to about 22° C., and said second heating temperature is about 69° C. to about 73° C.;
• e) cycling Step d) optionally one or more times, wherein the first cooling temperature at each cycle may be the same or different and the second heating temperature at each cycle may be the same or different;
• and
• f) cooling said suspension to a final cooling temperature to form said crystalline free-plate habit of L-arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid;
• wherein said final cooling temperature is about 18° C. to about 22° C.