Application of Differential Scanning Calorimetry to the Estimation of Drug Purity: Various Problems and Their Solutions in Purity Analysis.

Abstract

To establish conditions for differential scanning calorimetry (DSC) purity analysis, problems of instrumental differences, sample size, heating rate and details of the calculation of such analysis were examined. Two kinds of DSC instruments were used to examine instrumental differences, and changing the sample size or heating rate resulted in a difference in the effect of purity value between these two instruments. The analytical region in the linearization of the van't Hoff plot influenced the purity result, while calibration of the heat resistance using indium had little effect. A calculation without a eutectic peak area caused an overestimation of the purity.According to the above examination, the appropriate conditions for purity determination with our instruments were 1.0±0.1 mg sample size, 2.0°C/min heating rate and the linearizing region in the van't Hoff plot 10-50% of peak height. Applying this technique to some doped model drugs, acetaminophen, nicotinamide and ethenzamide, impurities of under 2mol% were accurately estimated except for acetaminophen. Acetaminophen was unsuitable for this method, because overlap of the melting peak and the other phase transitions was detected by modulated DSC.