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

Wissing, Sylvia, Craig, Duncan Q. M., Barker, Susan A. and Moore, William D. (2000) An investigation into the use of stepwise isothermal high sensitivity DSC as a means of detecting drug-excipient incompatibility. International Journal of Pharmaceutics, 199 (2). pp. 141-150. ISSN 0378-5173

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The use of stepwise isothermal high sensitivity differential scanning calorimetry (HSDSC) as a novel means of detecting excipient incompatibility is described using aspirin mixes with magnesium stearate and stearic acid as model systems. Aspirin, magnesium stearate and stearic acid alone and as mixes were studied in scanning mode using conventional DSC and were then subjected to a stepwise heating programme using HSDSC, whereby the samples were heated 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 kinetic 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 DSC represents a potentially highly useful means of detecting excipient incompatibilities. (C) 2000 Elsevier Science B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: compatibility,aspirin,screening,solid-state stability,stability,differential scanning calorimetry,ketoprofen,magnesium stearate,stearic acid,compatibility,technique,differential scanning calorimetry,excipient
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Rachel Smith
Date Deposited: 11 May 2011 11:14
Last Modified: 09 Aug 2023 12:30
DOI: 10.1016/s0378-5173(00)00380-x

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