In vivo evaluation of directly compressible spherical crystals of Celecoxib
By V. Rama Mohan Gupta, K Srikanth, B. Sree Giri Prasad, G. Naveen Kumar Reddy and B. Sudheer
Celecoxib spherical agglomerates were prepared with polyvinylpyrrolidone (PVP) using acetone, water and chloroform as solvent, non-solvent and bridging liquid, respectively. The agglomerates were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), IR spectroscopic studies and scanning electron microscopy (SEM). The IR spectroscopy and DSC results indicated the absence of any interactions between drug and additives. XRD studies showed a decrease in crystallinity in agglomerates. The crystals exhibited significantly improved micromeritic properties compared to pure drug. The loading efficiency (% or mg drug per 100 mg crystals) was in the range of 93.9 ± 2.3 and 97.3 ± 1.3% (n = 3) with all formulations. The aqueous solubility and dissolution rate of the drug from crystals was significantly (p < 0.05) increased (nearly two times). The solubility and In vitro drug release rates increased with an increase in PVP concentration (from 2.5 to 10%). The SEM studies showed that the crystal posseses a good spherical shape with smooth and regular surface. Based on these results, formulation prepared using 10% w/v PVP K 30 selected as optimized formulation. In vivo studies carried out on human volunteers with optimized formulation and the pharmacokinetic parameters were compared with marketed formulation. The celecoxib spherical crystals have shown enhanced therapeutic activity than the marketed formulation.
Key words: Celecoxib, spherical crystallization, solubility, dissolution rate, micromeritic properties, In vivo evaluation
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