Analysis of a mixture containing ampicillin anhydrate and ampicillin trihydrate by thermogravimetry, oven heating, differential scanning calorimetry, and X-ray diffraction techniques

Because the solubility of ampicillin anhydrate is quite different from that of ampicillin trihydrate, four basic techniques were employed to rapidly and precisely quantify mixtures of ampicillin anhydrate and ampicillin trihydrate. Using thermogravimetry and oven heating in a porcelain crucible, their ratio in mixtures was precisely quantified according to weight loss of water from ampicillin trihydrate in the mixtures. The ratio was also quantified based on the enthalpy change of water in ampicillin trihydrate and the phase change of ampicillin itself as measured by a differential scanning calorimeter. The X-ray diffraction intensity ratio of the mixtures at two specific angles was shown to be proportional to the ratio of the mixtures. Accordingly, a linear relationship between a change of physicochemical properties and a selected ratio of the mixtures was established. Comparison of the sample used, the R^2 value from linear curve-fitting, the maximum error and maximum measure limit in different techniques is also presented.