USE OF ISOTHERMAL HEAT-CONDUCTION MICROCALORIMETRY TO EVALUATE STABILITY AND EXCIPIENT COMPATIBILITY OF A SOLID DRUG

Isothermal heat conduction microcalorimetry was used to evaluate chemi cal stability and excipient compatibility of a solid drug. Calorimetri c data were compared with HPLC data in order to determine the origin o f the thermal events. For the pure solid drug, heat flow time curves b ecame constantly exothermic after 3-4 days in the temperature range fr om 60 to 80 degrees C and were due to chemical decomposition. The acti vation energy calculated by both methods (microcalorimetry and HPLC) w as 170 +/- 8 kJ/mol (mean +/- S.D.). A plot of the evolved heat Q vers us the amount of degraded drug showed a linear relationship. Binary mi xtures and granules led to higher exothermic signals for microcrystall ine cellulose (MCC), potato starch and lactose, and indicated lower st ability. In the case of MCC and lactose, physical processes were super imposed and made the interpretation of the heat flow data difficult. I n the case of the other systems the exothermic heat flow was in the sa me range as for the pure solid drug. Neither was physicochemical inter action 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. (C) 1998 Elsevier Science B.V. All rights reserved.