Solvent-mediated polymorphism and characterisation of inhaled pharmaceuticals

The use of polar anti-solvents for the crystallisation of lactose from 10% (w/v) aqueous solutions has been investigated. Crystal growth was observed at 50-65% antisolvent content and showed a morphological transition from polyhedral to needle-like habit with increasing antisolvent content, which coincided with a polymorphic transition from alpha lactose monohydrate (LαH2O) to beta lactose (Lβ). Where anhydrous dehydrating antisolvents were employed such as methanol and ethanol, evidence of Lα.H2O dehydration to form stable anhydrous alpha lactose (LαS) was also observed at 95% antisolvent content. Powder X-ray diffraction (PXRD) analysis of the samples 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 by PXRD. Application of the same crystallisation procedures to a racemic mixture of the active pharmaceutical ingredient (API) salbutamol sulfate (SS) indicated that some conditions can promote the formation of solvated SS......