An investigation into the use of stepwise isothermal high sensitivity DSC as a means of detecting drug-excipient incompatibility

The use of stepwise isothermal high sensitivity differential scanning calor imetry (HSDSC) as a novel means of detecting excipient incompatibility is d escribed using aspirin mixes with magnesium stearate and stearic acid as mo del systems. Aspirin, magnesium stearate and stearic acid alone and as mixe s were studied in scanning mode using conventional DSC and were then subjec ted to a stepwise heating programme using HSDSC, whereby the samples were h eated to temperatures between 45 and 70 degrees C and held for 1 h, during which the heat flow to or from the sample was measured. The data indicated that while no thermal events were detected for the individual components or mixes with stearic acid other than melting of stearic acid, 50% w/w mixes of magnesium stearate showed a marked endothermic response at temperatures above 55 degrees C. The data were fitted to an adaptation of an existing ki netic model for the degradation process and a reasonable correlation found. Mixes of the drug with the two excipients were then studied at 60 degrees C over 6 h at concentrations between 1 and 50% w/w. Incompatibilities with magnesium stearate concentrations as low as 1% w/w could be detected using this approach. Compacts of magnesium stearate and aspirin were also studied , with considerably more pronounced thermal events taking place compared to the powder mixes. It is concluded from these studies that while the study has highlighted certain limitations of the approach, stepwise isothermal DS C represents a potentially highly useful means of detecting excipient incom patibilities. (C) 2000 Elsevier Science B.V. All rights reserved.