Formulation and statistical optimization of clozapine solid self emulsification system for improving the dissolution properties

Abstract

Clozapine is an atypical antipsychotic drug that exhibits low bioavailability (>27%) due to poor solubility and higher hepatic metabolism. The present investigation was aimed to prepare a solid self-emulsifying drug delivery system (S-SEDDS) of clozapine to improve its dissolution properties. Various long-chained natural dietary oils, surfactants, and cosurfactants were screened to evaluate their drug solubilization ability and emulsification efficiency which was measured in terms of % transmittance of the formed system. A ternary phase diagram was generated to identify compositions that were able to form emulsions with the required globule size. The simplex lattice design was used to understand the effect of change in the composition of excipients on important product characteristics. The regression analysis suggested a significant effect of the change in the proportion of composition on selected response variables. The Liquid-SEDDS (L-SEDDS) were mixed with solid carriers (aerosil-200 and MCC) to form S-SEDDS. The results of Differential Scanning Calorimetry (DSC) and Powder X-Ray Diffraction (PXRD) studies indicated the complete transformation of the crystalline drug into the amorphous or molecular level dispersed state for the S-SEDDS prepared using aerosil-200 as a carrier. The results of in-vitro dissolution studies proved significant improvement in the dissolution of the drug from the S-SEDDS compared to the pure drug.