Experimental design aids the development of a differential scanning calorimetry standard test procedure for pharmaceuticals

Differential scanning calorimetry (DSC) is one of the important thermoanalytical techniques for preformulation studies of pharmaceutical substances. DSC studies can be used to characterize the melting behavior, crystallization, solid–solid transitions and chemical reactions of drugs. The attainment of proper results in a DSC experiment is dependant on a number of factors. The purpose of this study was to establish the appropriate condition for DSC performance. Factorial design and matrix analysis was used extensively in this study. The variables considered in this study were the sample size, heating rates, atmosphere, crucible type and relative humidity (RH). Two model drugs, benzoic acid (typical melting range: 121–123 °C, heat of fusion: 147 J/g) and vanillin (typical melting temperature: 81–83 °C, heat of fusion: 135 J/g) with sample size ranges of 3–5 and 10–12 mg were exposed to heating rates of 2 and 10 °C/min with atmospheres of air and nitrogen. The crucible types evaluated were open crucibles, crimped crucibles without pinhole and crimped crucible with pinhole. The samples were stored under 0, 25, 60 and 100% RH to evaluate the effect of RH on DSC performance. The study in this laboratory established a general protocol for DSC performance, which included the use of a small sample size range (3–5 mg), a low heating rate (2 °C/min), nitrogen as the atmosphere, crimped crucible without pinhole, and storage of the samples in a dry atmosphere (0% RH). Exceptions to the established protocols under various conditions are also discussed.