Mechanochemical Synthesis of Olanzapine Salts and Their Hydration Stability Study Using Powder X-ray Diffraction

A series of olanzapine (OLN) dicarboxylic acid salts including earlier reports on olanzapinium malonate (1:1) and maleate (1:1 and 1:2) were prepared mechanochemically using liquid assisted grinding (LAG) in order to study their hydration stability. Powder X-ray diffraction was used as a characterization tool during the investigation. On the basis of the single crystal structures of respective OLN salts, a negative correlation between the dicarboxylic acid chain length and the hydration stability of the corresponding OLN salt was found. Our observations suggest that the overall crystal packing, beyond the stronger hydrogen bond synthon (N+–H···O– in OLN salts compared to O–H···N in OLN hydrates) plays an important role in designing OLN salts with better hydration stability. In addition, melting point analysis showed that OLN dicarboxylic acid salts follow melting point alteration behavior similar to the pure diacids.