Application of a Mixture Experimental Design in the Optimization of the Formulation of Solid Self-Emulsifying Drug Delivery Systems Containing Carbamazepine

Abstract

The purpose of this study was to investigate the solid self-emulsifying drug delivery system (SSEDDS), as a potential delivery system for poorly water soluble carbamazepine by application of mixture design. The self-emulsifying drug delivery system (SEDDS) was formulated using Polysorbate 80, Transcutol (R) HP and Mygliol (R) 812. The input parameters for mixture design (components of SSEDDS) were: appropriate SEDDS, carbamazepine and adsorbent, Neusilin (R) UFL2, with appropriate ranges 10-30%, 30-50% and 40-60%, respectively. The output parameters were the percentages of carbamazepine released after 10 and 30 min. The aim was to formulate SSEDDS with very fast drug release, i.e. more than 80% of carbamazepine has to be released in 30 min. Optimal formulations were examined through the dissolution test, parallel artificial membrane permeability assay (PAMPA), differential scanning calorimetry and thermal gravimetric analysis. With the obtained mixture design models, for any combination of factors ratios, it is possible to predict the profile of carbamazepine release. Optimal formulations exhibited significantly improved drug release and permeability.