Capecitabine

Capecitabine is an anti-metabolite class of anti-neoplastic drug that is converted to fluorouracil in body tissue. Numbers of stability indicating chromatography method such as HPLC, HPTLC etc. have been reported for stability study of capecitabine. But the chromatography methods are tedious, time and solvent consuming methods. Hence, stability-indicating UV-visible spectroscopy method has been developed for hydrolytic degradation kinetic study of capecitabine using design of experiments (DoE)-based enhanced quality by design approach (QbD) to save time, solvent and cost of analysis. The potential method parameters were identified and assessed by risk priority number (RPN) ranking and filtering. The DoE-based full factorial designs were applied for degradation kinetic study in alkaline and acidic medium at different temperature. The rate constant, order of reaction, half-life and % degradation of capecitabine was calculated. The absorbencies of all samples were measured at 307nm wavelength and linearity of capecitabine was found to be in the range of 5-25µg/mL. The order of reactions for alkaline and acidic degradation kinetic was found to be first order. The highest degradation rate constant and % degradation of capecitabine was found to be in 0.3 N acid or base at 50?C. The prediction of rate constant and % degradation of capecitabine was done using DoE-based response surface analysis. The data of degradation kinetic was found to be in good agreement with published RP-HPLC method of capecitabine.

The goal of this study was to develop and optimize the Capecitabine loaded chitosan nanoparticles (CS-NPs)for improved colon cancer therapy, by enhancedsurface area, sustained drug release, reduced dose and hence, most importantly, reduced toxicity. Capecitabine loaded Chitosan nanoparticles were prepared by 32 full factorial designs, using ionotropic gelation method by cross-linking of chitosan (CS) with sodium tripolyphosphate (TPP). CS-NPs were prepared by dissolving chitosan in 1% (w/v) acetic acid solution under magnetic stirring at room temperature. The CS solution was diluted with deionized water to produce different concentration. The capecitabine was dissolved in CS solution using sonication and aqueous TPP solution was added drop wise using syringe to the mixture with moderate stirring for 30 min. The prepared nanoparticles were characterized by FT-IR spectroscopy and DSC to confirm the cross linking reaction between CS and cross-linking agent. From the % entrapment of capecitabine, nanoparticles were optimized using regression analysis, contour plots and check point analysis.Particle size of the optimized batch (CS-NPs-8) was found to be 87 nm. The Polydispersity index of the nanoparticles was found to be 0.113. The nanoparticles formed were spherical in shape with high zeta potentials, -35mV. In vitro release studies in phosphate buffer saline (pH 7.4) showed an initial burst effect and followed by a slow drug release. The drug release followed first order kinetics and was found to be diffusion controlled. Optimized formulation was also showing more % inhibition than drug alone in In-vitro anticancer study. From the accelerated study of optimized batch, it was found to be stable.