13 - Formulation development and in vitro multimedia drug release study of solid self-microemulsifying drug delivery system of ketoconazole for enhanced solubility and pH-independent dissolution profile

Abstract

The main aim of this research work was to develop and characterize solid oral self-microemulsifying drug delivery system (SMEDDS) for very low water-soluble drug ketoconazole (logP 4.4). Preformulation studies include the determination of equilibrium solubility of ketoconazole in different oils, surfactants, and cosurfactants. Drug–excipient compatibility was evaluated by using Fourier transform-infrared (FTIR) and differential scanning calorimetry (DSC) analysis. Microemulsion region was selected by pseudo-ternary phase diagrams using water titration technique. The optimized SMEDDS was formulated using Chremophor EL as surfactant, Capriol 90 as oil phase and Labrasol with Transcutol P in the ratio of 1:1 as cosurfactants. Spray drying was used to transform liquid SMEDDS into solid SMEDDS with Aerosil 200 as an inert solid carrier. The final formulation was thoroughly characterized for macroscopic evaluation, visual assessments, self-emulsification property, transmittance test, droplet size, zeta potential, thermal and crystallographic analysis, drug content determination, in vitro drug dissolution studies, surface morphology, and stability studies as per ICH guidelines. DSC and FTIR analysis exhibited drug–excipient compatibility. The formulation exhibited nearly 100% transmittance after dilution indicating transparent microemulsion. Cumulative drug release was measured spectrophotometrically which was more than 90% in 1h. The optimized formulation showed pH-independent dissolution profile. DSC and X-ray diffraction study confirmed that the ketoconazole was in the solubilized form. In conclusion, solid SMEDDS of ketoconazole for oral delivery was developed with excellent drug solubilization indicating enhanced solubility, drug stability, and pH-independent drug release.