Polymorphism Study of GW501516

Crystalline white powder of GW501516 was received from Wuhan Shu Mai Technology Co. (Wuhan, China) and solvents from Sigma-Aldrich and Merck, Taufkirchen, Germany. To obtain new polymorphs, a screening was undertaken in a variety of solvents and solvent mixtures. GW501516 (10 mg) with a purity of 99% was dissolved in a wide range of solvents (1 mL) after which the solutions were heated to approximately 40 °C and were allowed to cool to 3 °C. The vials were covered with parafilm in which very small holes were made; the solvents were left to evaporate slowly for several weeks.
The complete list of solvents used is the following: tetrahydrofuran, 2,2,2-trifluoroethanol, 1-butanol, diisobutyl ketone, dimethylformamide, ethyl acetate, 1-propanol, chloroform, 2-ethoxyethanol, 1,4-dioxane, methanol, acetone, nitromethane, ethanol, dichloromethane, dimethylacetamide, dimethylformamide, pentane, acetic acid, methyl isobutyl ketone, diisopropyl ether, and isopropyl alcohol.
The solvent mixtures used for polymorph screening were 1:1 volumetric ratios of 2,2,2-trifluoroethanol with tetrahydrofuran, methanol with tetrahydrofouran, ethyl acetate with dimethylformamide, chloroform with isopropyl alcohol, ethyl acetate with acetone, diisopropyl ether with acetic acid, and pentane with acetone.
In this way, the polymorphs were obtained as follows:(i)

GW-1 (starting polymorph) from acetonitrile;

(ii)

GW-2 from mixture of pentane and acetone;

(iii)

GW-3 in isopropyl alcohol;

(iv)

GW-5 in methyl isobutyl ketone;

(v)

GW-4 was found in the bulk of the starting sample as single crystals but was not further reproduced.