Preparation, characterization and in vitro dissolution studies of solid systems of valdecoxib with chitosan

In the present study, the solubilizing and amorphizing properties of Valdecoxib (a poorly water soluble anti inflammatory drug) with low molecular weight chitosan (a polymer), have been investigated. Binary systems of varying drug/polymer ratios were prepared using different techniques (physical mixing, co-grinding, kneading) and were tested for dissolution. Drug carrier interactions were investigated in both the liquid and solid state, by phase solubility analysis, differential scanning calorimetry, powder X-ray diffractrometry, FT-IR spectroscopy and scanning electron microscopy. The solubility of the drug increased with increasing polymer concentration showing A(N) type phase solubility diagram. Differential scanning calorimetry, powder X-ray diffractrometry and scanning electron microscopic studies of binary systems suggested generation of amorphous form of drug (in kneading and co ground mixtures). IR spectroscopy revealed the presence of hydrogen bonding in kneading and co ground mixtures. Drug dissolution was improved with increasing the polymer concentration in the mixture (Kneaded>co ground>physical mixture), which was attributed to the amorphonization and/or decreased drug crystallinity, size and polymer wetting effect. Enhanced dissolution combined with its direct compression feasibility and anti ulcerogenic action results in low molecular weight chitosan for developing fast release oral solid dosage forms of valdecoxib.