Preparation and characterizations of stable amorphous solid solution of azithromycin by hot melt extrusion

Abstract

In the present study aim was to prepare stable solid solution azithromycin dihydrate (AZI) by hot melt extrusion technology (HME). Soluplus and Kollidon® VA 64 were selected among polymers based on Hansen solubility parameter calculation in order to prepare amorphous of AZI. Further physicochemical properties of extrudates were characterized by DSC, FTIR, XRD, SEM and contact angle measurement. DSC revealed single broad endothermic peak in extrudates indicated miscibility of AZI into polymeric carriers, which formed monophasic solid system termed as solid solution. XRD confirmed amorphous nature of AZI in extrudates. DSC and XRD suggested molecular dispersion of AZI in polymeric carriers. Amorphous AZI exhibited statistically significant high solubility (P < 0.0001) in water in comparison with pure AZI. Solid solution batch AZI 03 showed significant enhancement in solubility (P = 0.0004) in pH 6. The dissolution in dissolution medium pH 6 and water resulted in statistically significant differences (P < 0.05) in the percentage amorphous AZI dissolved compared to the percentage AZI dissolved over the period of 60 min. Solid solution formulation showed better wettability than that of pure AZI. Amorphization and increased wettability attributed to solubility and dissolution rate enhancement. Assay and amorphous solid solution characteristics of AZI were found to be stable under accelerated storage condition as per ICH guideline for a period of six months. Therefore, hot melt extrusion technology was suitable method to prepare stable solid solution and dissolution rate enhancement for poorly soluble active like AZI.