Crystallization of paracetamol from solution in the presence and absence of impurity

The bulk crystallization of paracetamol has: been examined under controlled conditions in the presence and absence of the additive p-acetoxyacetanilid e (PAA), as a function of both supersaturation and additive levels. The ind uction time to nucleation was found to increase with increase in PAA concen tration in solution. The product micro-crystals were characterized for shap e and strain/defect content using electron and optical microscopy and X-ray Laue diffraction techniques, respectively. A change in crystal habit of th e pure crystals from columnar (dominant {110}) to plate-like (dominant {001 }) was observed to occur with an increase in supersaturation level, whilst the addition of PAA invariably led to the development of columnar crystals with an aspect ratio that varied with impurity level and supersaturation. H PLC showed the PAA to be incorporated into the crystals with an average seg regation coefficient of 14-18% depending on the supersaturation. The ready incorporation of PAA is attributed to the molecular similarity of this mole cule to that of the host material. The incorporation is shown to cause a si gnificant increase in the mosaic spread, implying the development of a sign ificant strain/defect content in the crystals. The influence of the impurit y on the time to nucleation is probably due to its effect in blocking the d evelopment of the critical nucleus. The potential implications of such vari ations in morphology and strain content in the design of the physical and c hemical properties of the resulting particulates are discussed. (C) 2001 El sevier Science B.V. All rights reserved.