Preparation, Characterization and Optimization of Poloxamer Solid Dispersions of a Poorly Water Soluble Drug Aprepitant

Aim: The aim of the present investigation was to enhance the dissolution rate of a poorly water soluble drug, aprepitant, by preparation of solid dispersion with hydrophilic carrier, poloxamer 188, using solvent evaporation method.
Place and Duration of Study: Department of Pharmaceutical Sciences and Department of Emerging Life Sciences, Guru Nanak Dev University, Amritsar, Punjab, between August 2012 and July 2013.
Study Design: Designs of experiments were carried out with two input variables, drug to carrier ratio (X1) and amount of solvent (X2). A total of 7 experiments were performed (4 factorial runs and 3 centre points) as per full factorial design. Percent dissolution efficiency at 60 min (DE60) was selected as the response variable. Pareto chart along with half probability plot were studied for determining the most significant process variables, which were modelled using ANOVA.
Methodology: Solid dispersions of aprepitant with poloxamer 188 were prepared using the solvent evaporation method and studied systematically using an optimization technique. A 22 full factorial design approach was used for the optimization of process variables on dissolution characteristics. The optimized solid dispersion was characterized by dissolution studies, Fourier Transform Infrared Spectroscopy, Differential Scanning Calorimetry, X-ray powder Diffraction studies and Scanning Electron Microscopy.
Results: The results of the experimental study confirm that the factors like drug to carrier ratio and solvent amount significantly influence the dependent variable DE60. A high level of drug to carrier ratio and low level of solvent amount were found to be suitable for maximum DE60. The use of factorial design approach helped in the optimization of the solid dispersion. The characterization of optimized solid dispersion (F5) demonstrated that the decrease in crystallinity of aprepitant and poloxamer 188 might be responsible for the enhanced dissolution rate. Analysis of dissolution data indicated the best fitting with first-order model.
Conclusion: Dissolution enhancement of aprepitant was successfully obtained by preparing its solid dispersion with poloxamer 188 using solid evaporation method.