Crystalline forms of quetiapine hemifumarate

A method of making crystalline quetiapine hemifumarate having at least one characteristic of form II comprising the steps of:

• a) treating quetiapine hemifumarate with a treating solvent selected from chloroform and methylene chloride, and
• b) isolating the crystalline quetiapine hemifumarate having at least one characteristic of form II.

Crystalline quetiapine hemifumarate form II dichloromethane solvate characterized by x-ray reflections at 7.8°, 11.9°, 12.5°, 15.7°, 23.0°, and 23.4°,±0.2° 2θ, absorption bands in FTIR at 639, 1112, 1395, 1616, 1711, and 3423 cm−1, and a thermogram in differential scanning calorimetry having endothermic peaks at about 130° C. and about 166° C.

Crystalline quetiapine hemifumarate form II chloroform solvate characterized by x-ray reflections at 7.8°, 11.9°, 12.5°, 15.7° 23.0°, and 23.4°,±0.2° 2θ, absorption bands in FTIR at 639, 1112, 1395, 1616, 1711, and 3423 cm−1, and a thermogram in differential scanning calorimetry having endothermic peaks at about 130° C. and about 166° C.

A crystalline form of quetiapine hemifumarate having at least one characteristic selected from the group consisting of:

• 1) x-ray reflections at about 8.9°, 11.8°, 15.3°, 19.4°, 23.0°, and 23.4°,±0.2° 2θ,
• 2) absorption bands in FTIR spectroscopy at 748, 758, 1402, 1607, 1715, and 2883 cm−1, and
• 3) a DSC thermogram with endothermic peaks at about 111° C., about 142° C., and about 167° C.

Crystalline quetiapine hemifumarate form III chloroform solvate characterized by x-ray reflections at about 8.9°, 11.8°, 15.3°, 19.4°, 23.0°, and 23.4°,±0.2° 2θ, and absorption bands in FTIR at 748, 758, 1402, 1607, 1715, and 2883 cm−1.

A method of making crystalline quetiapine hemifumarate form I comprising the steps of:

• a) providing a solution at about 80° C. of quetiapine hemifumarate in a solvent selected from the group consisting of water, alkanol, and dipolar aprotic solvents,
• b) combining the solution with an anti-solvent whereby a suspension is obtained, and
• c) isolating quetiapine hemifumarate form I from the suspension.

A method of making crystalline quetiapine hemifumarate form I comprising the steps of:

• a) providing a solution at about 80° C. of quetiapine hemifumarate in a solvent selected from the group consisting of alkanol, and a combination of a dipolar aprotic solvent and water,
• b) cooling the solution to a temperature of about 20° C. or less, and
• c) isolating the quetiapine hemifumarate form I from the mixture.

A method of treatment comprising administering to a mammal the pharmaceutical composition including one or more of quetiapine hemifumarate form II chloroform solvate, quetiapine hemifumarate form II dichloromethane solvate and quetiapine hemifumarate form III chloroform solvate, and at least one pharmaceutically acceptable excipient.

A crystalline form of quetiapine hemifumarate characterized by x-ray reflections at 11.9°, 12.5°, 14.6°, 15.7°, and 16.8°,±0.2° 2θ.

A crystalline form of quetiapine hemifumarate characterized by x-ray reflections at 8.9°, 11.8°, 15.3°, 19.4°, 23.0°, and 23.4°,±0.2° 2θ.