Experimental and Theoretical Studies on Molecular Geometry and Polymorphism in Crystalline Drug Substances

Abstract

The phenomena of polymorphism and pseudo-polymorphism are introduced, together with their pharmaceutical importance. Some basic knowledge about rystallization is introduced as well as the methods of experimental structure determination. Theinformation about H-bonds and prediction of polymorphic forms is also given in the first chapter. The pharmaceutical role of Temozolomide and 5,5 diphenylhydantoin is introduced in the second chapter.Using aqueous acetic acid as solvent, we crystallized a hydrate of Temozolomide, and the same hydrate also grows in the water: acetone 1:1 mixed solvent. This hydrate has a space group of P21/m in a cell of dimensions a = 7.5158(9), b = 6.3044(13), c =9.5324(16) Å, β = 92.907(12), V = 451.09(13) Å3, Z)= 2. Its crystal structure wasdetermined by direct methods and refined by full-matrix least squares...