Statistical evaluation of nonisothermal prediction of drug stability.

Nonisothermal prediction of drug stability based on direct nonlinear estimation of the shelf-life was compared with the isothermal approach. The reliability of the statistics for the estimates of the shelf-life (the time period required for a drug to degrade to 90% remaining at 25 degrees C) and activation energy obtained by the two methods was evaluated by the Monte Carlo method of computer simulations. The accuracy and precision of the estimates obtained by the nonisothermal method depended largely on the experimental conditions, such as experimental periods, sampling time, and temperature rise programs. The uncertainty of the estimates was determined mainly by the extents of drug degradation and temperature change achieved during the experiment. The nonisothermal method needed suitable experimental designs and precise assay methods of drug contents to provide reliable parameter estimates.