EFFECTS OF GRINDING AND HUMIDIFICATION ON THE TRANSFORMATION OF CONGLOMERATE TO RACEMIC COMPOUND IN OPTICALLY-ACTIVE DRUGS

The effects of grinding and humidification on the transformation of co nglomerate to racemic compound have been investigated by X-ray powder diffraction (XPD), differential scanning calorimetry (DSC) and infrare d (IR) spectroscopy for leucine, norleucine, valine, serine, tartaric acid and malic acid. Racemic physical mixtures were prepared by physic al mixing of equimolar quantities of D and L crystals using a mortar a nd pestle. Ground mixtures were obtained by grinding the physical mixt ures with a vibrational mill. Humidification was performed by storing the physical mixtures and the ground mixtures in a desiccator containi ng saturated aqueous salt solutions at 40 degrees C. When physical mix tures of malic acid, tartaric acid and serine were ground, the XPD pea ks of the racemic compounds were observed. The XPD patterns of humidif ied physical mixtures of these compounds also showed the formation of the racemic compounds. This indicated that grinding or humidification of malic acid, tartaric acid and serine induced the transformation of conglomerate to racemic compound crystals. When, on the other hand, th e physical mixtures of valine, leucine and norleucine were ground, pea ks of racemic compounds were not detected in the XPD pattern. After hu midification of the ground mixtures of valine, leucine and norleucine, however, the XPD peaks of racemic compounds were observed. DSC and IR studies revealed consistent results. We concluded that grinding or hu midification of malic acid, tartaric acid and serine could induce the transformation of a conglomerate to racemic compound. In contrast, hum idifying after grinding was needed to bring about the transformation i n leucine, norleucine and valine.