Characterization of Commercial Lots of Erythromycin Base

Abstract

The physical properties of five commercial lots of erythromycin base were evaluated with the object of characterizing the bulk chemical. The materials were investigated by thermal analyses, IR spectroscopy, Xray powder diffractions, equilibrium solubility in distilled water, and dissolution rates in phosphate buffer pH 7.5. Among the lots examined, three were found to be polymorphic variants of crystalline dihydrate, one a crystalline anhydrate and the other an amorphous solid. The different crystalline dihydrates displayed considerable variation in thermal properties but showed similar equilibrium solubilities in distilled water. At a given temperature, crystalline anhydrate has a higher aqueous solubility compared to the dihydrates. All crystalline forms of erythromycin showed rapid in vitro drug release from loosely-filled capsules. In contrast, the amorphous form exhibited a high equilibrium solubility but slower dissolution rate, a result attributable to its poor wettability. Contact angle measurements performed on powder compacts of the solid confirmed the hydrophobic nature of the amorphous form, an inference based on the high and stable contact angles formed. Under similar test conditions, low contact angles and rapid spreading of liquid film were noted for the crystalline dihydrates. The previously reported observations of lower solubility with increasing temperature was confirmed in the current studies for all forms of erythromycin base.