Use of isothermal heat conduction microcalorimetry to evaluate stability and excipient compatibility of a solid drug

Abstract Isothermal heat conduction microcalorimetry was used to evaluate chemical stability and excipient compatibility of a solid drug. Calorimetric data were compared with HPLC data in order to determine the origin of the thermal events. For the pure solid drug, heat flow time curves became constantly exothermic after 3–4 days in the temperature range from 60 to 80°C and were due to chemical decomposition. The activation energy calculated by both methods (microcalorimetry and HPLC) was 170±8 kJ/mol (mean±S.D.). A plot of the evolved heat Q versus the amount of degraded drug showed a linear relationship. Binary mixtures and granules led to higher exothermic signals for microcrystalline cellulose (MCC), potato starch and lactose, and indicated lower stability. In the case of MCC and lactose, physical processes were superimposed and made the interpretation of the heat flow data difficult. In the case of the other systems the exothermic heat flow was in the same range as for the pure solid drug. Neither was physicochemical interaction detected, nor was the chemical decomposition accelerated by the excipients. By combining calorimetric and HPLC data the prediction of final shelf-life at room temperature was estimated.