Antisolvent crystallization of pharmaceutical excipients from aqueous solutions and the use of preferred orientation in phase identification by powder X-ray diffraction

Crystallization of lactose from 10% (w/v) aqueous solutions was investigated with the use of polar antisolvents. Crystal growth was observed at 50–65% antisolvent content and showed a morphological transition from a polyhedral to needle-like habit with increasing antisolvent content, which coincided with a polymorphic transition from alpha lactose monohydrate (Lα·H2O) to beta lactose (Lβ). Where dehydrating antisolvents were employed such as methanol and ethanol, evidence of Lα·H2O dehydration to form LαS was also observed at 95% antisolvent content. Powder X-ray diffraction (PXRD) analysis of the crystals highlighted the preferred orientation effects exhibited by large crystals of this kind, indicating the difficulties experienced by the non-specialist when performing phase identification of lactose polymorphs. The same studies were applied to raffinose pentahydrate, trehalose dihydrate and mannitol to assess the effects of crystallization conditions on other pharmaceutical excipients.