FORMULATION AND CHARACTERISATION OF AZITHROMYCIN DIHYDRATE INCLUSION COMPLEXES USING DERIVATIVES OF $\lambda$-CYCLODEXTRINS AS COMPLEXING AGENTS

Abstract

In the present research, an attempt was made to study enhancement of solubility and bioavailability of azithromycin, a sparingly water soluble macrolide antibiotic, by use of inclusion complexation technique, using 1:1 and 1:2 w/w ratios of three complexing agents-$\beta$-cyclodextrin, epichlorohydrin-$\beta$- cyclodextrin and sulfobutylether cyclodextrin. Two methods were used - solvent evaporation and freeze drying/lyophilisation. Drug – excipients incompatibilities were studied using Fourier transform Infra-red spectroscopy and Differential scanning calorimetry. IR spectra did not show any significant changes in characteristic peaks of pure drug and excipients. DSC thermograms showed characteristic endothermic peaks at respective melting points of pure drug and excipients, thus ruling out of any undesirable interactions. Drug content of all prepared 12 inclusion complexes ranged from
97.4 - 99.5 %. Prepared inclusion complexes were characterised using In-Vitro dissolution studies, kinetic modelling patterns, Scanning electron microscopy images and X Ray Diffractograms. In Vitro drug profiles showed 96 % drug release for inclusion complexes using Sulfobutyl ether $\beta$- cyclodextrin, prepared using freeze drying method. From the kinetics, it could be possibly stated that the release from the matrix was through diffusion. The XRD pattern depicted by optimised complexes reveals a decrease in the number of 20 peaks which probably represents decrease in crystallinity. SEM images also showed the nature of particles to be highly porous. Thus, it can be concluded that, Inclusion complexation technique using freeze drying method, and newer derivatives of $\beta$-cyclodextrin as complexing agents has proven to be highly effective in improving bioavailability of poorly water-soluble drugs than $\beta$ – Cyclodextrin alone.