Amorphous azithromycin with improved aqueous solubility and intestinal membrane permeability

Abstract

Azithromycin (AZM) is a poorly soluble macrolide antibacterial agent. Its low solubility is considered as the major contributing factor to its relatively low oral bioavailability. The aim of this study was to improve the solubility of this active pharmaceutical ingredient (API) by preparing an amorphous form by quench cooling of the melt and to study the influence of the improved solubility on membrane permeability. The amorphous azithromycin (AZM-A) exhibited a significant increase in water solubility when compared to the crystalline azithromycin dihydrate (AZM-DH). The influence that the improved solubility could have on membrane permeability was also studied. The apparent permeability coefficient (Papp) values of AZM-A were statistically significantly higher (p < 0.05) than crystalline AZM-DH at pH values of 6.8 and 7.2. The results therefore indicated that the improved solubility of AZM in the amorphous form also produced improved permeability across excised intestinal tissue at physiological pH values found in the small intestine.

Keywords: Amorphous; apparent permeability coefficient; azithromycin; dissolution; solubility; vapor sorption.