This article investigates enhancement of the dissolution profile of valdecoxib using solid dispersion with PVP. The article also describes the preparation of fast-dissolving tablets of valdecoxib by using a high amount of superdisintegrants. A phase solubility method was used to evaluate the effect of various water-soluble polymers on aqueous solubility of valdecoxib. Polyvinyl pyrrolidone (PVP K-30) was selected and solid dispersions were prepared by the method of kneading. Dissolution studies using the USP paddle method were performed for solid dispersions of valdecoxib. Infrared (IR) spectroscopy, differential scanning calorimetry (DSC), and x-ray diffractometry (XRD) were performed to identify the physicochemical interaction between drug and carrier, hence its effect on dissolution. Tablets were formulated containing solid dispersion products and compared with commercial products. IR spectroscopy, XRD, and DSC showed no change in the crystal structure of valdecoxib. Dissolution of valdecoxib improved significantly in solid dispersion products (< 85% in 5 minutes). Tablets containing solid dispersion exhibited better dissolution profile than commercial tablets. Thus, the solid dispersion technique can be successfully used for improvement of dissolution of valdecoxib.

Solubility enhancement of poorly aqueous soluble drug is an important aspect of formulation development. Although there is plethora of reports of solubility improvement using different techniques, a comparative study of different solubilization approaches are few. Valdecoxib chemically designated as 4-(5-methyl-3-phenyl-4-isoxazolyl) benzenesulfonamide is a novel potent COX-2 inhibitor having poor aqueous solubility (10 µg/ml). Since it is poorly water-soluble, various techniques could be applied to increase its aqueous solubility. Objective of present study was to provide a comparison of effect of various solubilization techniques, namely micellar solubilization, cyclodextrin complexation and cosolvency, on solubility of valdecoxib. Solubility of valdecoxib was determined in various ionic and nonionic surfactants using phase solubility analysis. Similar type of study was performed using different water:cosolvent mixture. In addition, solubility improvement by use of 2 novel hydrophilic β-cyclodextrin derivatives, hydroxypropyl β-cyclodextrin and sulfobutyl ether-7-β-cyclodextrin was examined. Results showed that highest solubility (70 fold) was achieved with use of Cremophor EL followed by Tween 80 and sulfobutyl ether-7-β-cyclodextrin. It was found that surfactants with higher HLB values were better solubilizers. Solubilization capacity was found to increase with increase in hydrocarbon chain of surfactant, suggesting hydrocarbon core of micelles as locus of solubilization. Similarly, less polar solvents were found to increase solubility by greater extent, thus accentuating hydrophobic interaction mechanism. Among cyclodextrin, higher binding constant and solubility enhancement was obtained by use of sulfobutyl ether-7-β-cyclodextrin. Thus, the study generated an important dataset so as to compare effect of various solubilizers on solubility of valdecoxib.