Applications of pressure differential scanning calorimetry in the study of pharmaceutical hydrates. II. Ampicillin trihydrate

Abstract

The dehydration of ampicillin trihydrate (C 16H 19N 3O 4S·3H 2O) was studied by both conventional differential scanning calorimetry (DSC) and by pressure differential scanning calorimetry (PDSC). The solid state of the anhydrous phase formed was influenced by the DSC conditions. At ambient pressure, dehydration resulted in the formation of X-ray amorphous anhydrous ampicillin, while at elevated pressures a crystalline anhydrate was obtained. These conclusions were based on variable temperature X-ray powder diffractometry (VTXRD) which was used as a complementary technique. PDSC was a reliable technique to quantify the relative amounts of ampicillin trihydrate and anhydrous ampicillin when they occur as a mixture. Grinding-induced alterations in the degree of crystallinity of ampicillin trihydrate were also quantified by PDSC. The changes in crystallinity induced after milling for just 1 min were detected and quantified with a high degree of precision. PDSC appears to be an excellent technique not only for the characterization but also for obtaining quantitative information about the solid state of pharmaceutical hydrates.