Enhancement of Solubility and Dissolution Rate of a Poorly Water Soluble Drug Using Single and Double Hydrophilization Approach

The aim of present investigation was to improve the solubility and dissolution rate limited absorption of lornoxicam (LXM) by making solid complexes using single and double hydrophilization approaches. For this, effect of Polyvinylpyrrolidone K-30 (PVP K-30) and Poloxamer-407 (PXM407) auxiliary substances on complexation of drug with β-cyclodextrin was studied by investigating their interactions in solution and solid state. Phase solubility studies were done to evaluate the solubilizing efficiency of β-CD in association with auxiliary substances to determine stability constant (Ks) and complexation efficiency (CE). Improvement in Ks and CE by double hydrophilization approach evident the additive effect of auxiliary substances. PXM-407 was found to be the promising auxiliary substance in terms of getting optimum results. Solid dispersions by single and double hydrophilization approach were prepared by kneading, co-evaporation, microwave irradiation and lyophilization method. Double hydrophilized solid complexes were superior over single hydrophilized complexes in terms of higher solubility, CE, Ks, in-vitro dissolution rate and reduction in formulation bulk. Optimized solid complexes were characterized by SEM, DSC, XRD and FTIR spectroscopy. Lyophilized double hydrophilized complex of LXM-β-CD-PXM-407 indicated a significant improvement in the in-vitro dissolution rate as compared to solid complexes prepared by rest of the methods (p<0.05) due to porous and amorphous drug particles, reduction in total interfacial tension by PXM407 and formation of inclusion complex by β-CD. In a nut shell it can be concluded that lyophilized double hydrophilized complex was the most prominent approach to enhance the solubility and dissolution rate limited absorption of lornoxicam.