Microstructural investigation of nimesulide-crospovidone composites by X-ray diffraction and thermal analysis

Dispersion into crospovidone is a widely employed method for enhancing the solubility of poorly water-soluble drugs, since the 3D polymeric network stabilizes the active substance in molecular clusters and nano-crystalline phases. Nimesulide loaded into crospovidone shows two polymorphic modifications: the native material (form I) and the phase reported on ICDD and CSD databases (form II). Microstructure and polymorphism of the composites have been investigated as they affect the drug dissolution rate and in vivo absorption kinetics (i.e. the bio-availability of the drug from its dosage form). Differential scanning calorimetry (DSC) showed that the lower melting form (form II) is metastable. X-ray diffraction (XRD) evidenced that the embedded crystalline phases are made up of nano-crystallites and that no significant difference on their size exists. Quantitative analysis of the composites turned out to be a challenge with both XRD (preferred orientation effects and form I crystalline structure unknown) and DSC (high nimesulide-crospovidone reactivity). Nevertheless, the results suggest a direct correlation between crospovidone and form II weight fractions. (C) 2003 Elsevier Science Ltd. All rights reserved.