Design of experiments for the optimization of mefenamic acid microencapsulation in EC/HPMC cellulose derivatives and drug release improvement using β-cyclodextrin inclusion complex

Abstract

Mefenamic acid (MA) is one of the low water soluble non-steroidal anti inflammatory drugs (NSAID), exhibiting poor wetting and poor dissolution. MA forms with β-cyclodextrin supramolecular inclusion complexes approving a drug solubility enhancement. The aim of the study is to combine the solubilization capability of a supramolecule MA:b-CD with the complementary functional properties of Ethylcellulose (EC) and hydroxylpropylmethylcellulose (HPMC) hybrid coat for the development of new MA controlled drug delivery systems, by using emulsion-solvent evaporation technique. First, a 2² factorial design is drawn to prepare and optimize pure MA/HPMC:EC microspheres, by studying and evaluating the effect of HPMC:EC ratio (1:1 and 1:4) and stirring speed of emulsion (600 and 1000 rpm) on the drug entrapment. The results showed that the main effect of variables is statistically significant, the drug entrapment was improved using HPMC and varied from 20 to 39%. Second, MA:b-CD inclusion complex was prepared by solvent co-evaporation method and subsequently encapsulated into EC and EC/HPMC hybrid matrices. The in vitro drug dissolution tests were performed in phosphate buffer solution with pH=7.4 at 37°C and the results showed that the drug release was effectively increased for MA:b-CD inclusion complex loaded microspheres.