Optimization of fast melting olanzapine tablets using solid dispersion and response surface methodology

Abstract

Background: Olanzapine is a poorly water-soluble, anti-psychotic drug that belongs to the class of thiobenzodiazepines, which has a bioavailability of 60 – 65%. The purpose of this research work is to enhance the solubility of olanzapine by the solid dispersion technique using different water-soluble carriers, using a phase solubility study using a 2⁴ factorial design, and to incorporate the solid dispersion of olanzapine to formulate fast-melting tablets using different superdisintegrants. Methodology: The fast-melting tablets were prepared using the wet granulation technique and optimized through a 2³ full factorial design.  The independent variables are sodium starch glycolate (X1), sodium carboxymethyl cellulose (X2), and the method of preparation of the solid dispersion (X3).  The dependent variables are hardness (Y1), friability (Y2), disintegration time (Y3), and in vitro drug release studies (Y4). The kinship between independent and dependent variables was demonstrated using contour diagrams. Additionally, the prepared fast-melting tablets were analysed for their weight variation, drug content uniformity, and other dependent variables. Results and Discussion: The fast-melting tablets (batch F6) were considered desirable based on their drug content (99.5% & drug release of 99.3% in 20 minutes, following first–order and Higuchi kinetics. The difference factor f1and f2 similarity factor were found to be 2.43% and 83%, respectively, for the optimized formulation FM2, and the drug release was greater than that of the marketed product. Conclusion: It is evident that the optimized formulation FM2 appears to be a promising system that facilitates the rapid release of olanzapine compared to other formulations.