Crystal modification of dipyridamole using different solvents and crystallization conditions

Dipyridamole crystals having different types of habits, improved dissolution rate were prepared by recrystallization from selected solvents, such as acetonitrile, benzene and methanol (Method 1); crystals have also been made by solvent change using methanolic solution of dipyridamole in the presence of 2% solutions of Tween-80, Povidone K-30 and polyethylene glycol (PEG) 4000 (Method Iota Iota). Scanning electron microscopy, X-ray powder diffractometry, IR spectrometry and differential scanning calorimetry were used to investigate the physicochemical characteristics of the crystals. The comparative dissolution behavior of the newly developed crystals and that of the untreated dipyridamole were also studied. It was found that the newly developed crystals were different from each other with respect to physical properties but are chemically identical. The crystals, obtained (Method 1) from benzene and acetonitrile, produced needle shaped crystals and that obtained from methanol produced rectangular shaped crystals. But the crystals obtained (Method Iota Iota) with the methanolic solution of the drug in the presence of Tween-80, Povidone K-30 and PEG-4000 produced smooth needle shaped crystals. X-ray diffraction spectra and differential scanning calorimetry study of the newly developed crystals, clearly indicate that dipyridamole exist in different crystal modification. The dissolution rate of newly developed crystals was found to be greater than the pure drug dipyridamole. Stability studies at 40 degrees C (75% RH) for 1 month for the modified crystals as well as the pure drug did show some changes in the XRD and DSC but not in IR studies. (c) 2006 Elsevier B.V. All rights reserved.