PREPARATION AND CHARACTERIZATION OF ECONAZOLE NITRATE INCLUSION COMPLEX FOR OCULAR DELIVERY SYSTEM

Abstract

Objective: Econazole nitrate (ECZ) is one of the triazole antifungal drugs with poor aqueous solubility and dissolution rate; there is a need for enhancement of solubility. Therefore; inclusion complexation with β cyclodextrin (βCD) was performed.Methods: In this study kneading method and co-evaporation method of preparation of inclusion complex between βCD and ECZ using two molar ratios of βCD. The solubility of these complexes in isotonic saline solution and distilled water was studied. Complexes prepared by kneading method were used for the preparation of different ophthalmic gel formulas using carbomer (CB) and sodium carboxymethylcellulose (sod CMC) as a gelling agent. The release profile and the rheological behaviour of the gel were studied.Results: The solubility of ECZ was enhanced by complexation with β CD, and both complexation methods showed Ap type solubility curve, but the solubility of ECZ was significantly enhanced by complexation using kneading method over co-evaporation. EZC-βCD complex prepared by kneading method with 0.88 *10-3 MβCD molar ratio and formulated in a gel using CB 0.75% w/w and sod CMC 0.25% w/w may be considered as a good candidate for ECZ ophthalmic gel dosage form, which showed Super case II transport release profile, and pseudo-plastic shear thinning behavior.Conclusion: Kneading method was found to be the best method for inclusion of ECZ into βCD, which significantly enhanced ECZ solubility; enabling to be formulated into an ophthalmic gel using CB as a polymer, for further development.