No / Mannitol is a polymorphic pharmaceutical excipient, which commonly exists in three forms: alpha, beta and delta. Each polymorph has a needle-like morphology, which can give preferred orientation effects when analysed by X-ray powder diffractometry (XRPD) thus providing difficulties for quantitative XRPD assessments. The occurrence of preferred orientation may be demonstrated by sample rotation and the consequent effects on X-ray data can be minimised by reducing the particle size. Using two particle size ranges (<125 and 125¿500 ¿m), binary mixtures of beta and delta mannitol were prepared and the delta component was quantified. Samples were assayed in either a static or rotating sampling accessory. Rotation and reducing the particle size range to <125 ¿m halved the limits of detection and quantitation to 1 and 3.6%, respectively. Numerous potential sources of assay errors were investigated; sample packing and mixing errors contributed the greatest source of variation. However, the rotation of samples for both particle size ranges reduced the majority of assay errors examined. This study shows that coupling sample rotation with a particle size reduction minimises preferred orientation effects on assay accuracy, allowing discrimination of two very similar polymorphs at around the 1% level.

Curcumin is the major phenolic diarylheptane derivative in Curcuma longa and has been reported to possess pharmacological activities. Unfortunately this compound suffers from poor bioavailability and rapid neutral-alkaline degradation. Co-crystal of curcumin is one option under exploration, motivated by the fact that a number of active pharmaceutical ingredient (API) co-crystals with improved dissolution have recently been synthesized. Hence, co-crystallization technique highlights an alternative means to improve the performance of curcumin. Within our work evidences for a co-crystal was ascertained from DSC, Kofler hot stage screening and PXRD, and all confirmed a new crystal phase could have been formed between curcumin and a co-crystallizing agent, nicotinamide. We report that re-crystallization step essentially aids the purification of commercial curcumin, a herbal based actives. Otherwise the prevalence of a new crystal phase in solvent-mediated co-crystallization will be significantly reduced. Besides, phase diagram is an effective tool for the study of solubility behaviours in co-crystal system. In order to acquire related techniques, fenbufen, a poorly water soluble drug, was selected. The result showed the huge difference in solubility between fenbufen and nicotinamide lead to difficulty in the construction of phase diagram.