Application of Model-Free Kinetics to Some Pharmaceutical Stability Problems

摘要

Solid-state kinetics plays an important role in pharmaceutical stability. This studyrncompares the model-free and model-fitting approaches to some solid-state transformations ofrnpharmaceuticals.rnThe kinetics of three solid-state reactions, crystallization of amorphous nifedipine andrntwo consecutive steps in the dehydration of nedocromil sodium trihydrate, are described.rnModel-fitting analysis shows that several statistically equivalent models fit each study,rnwhile the fitted activation energy and the frequency factor strongly depend on the model fitted.rnTherefore, selection of the appropriate model is difficult. Results from the model-free approachrnshow that activation energy changes as the reaction proceeds for all three processes, indicatingrnchanges in the mechanisms. Numerically reconstructed experimental kinetic functionsrndemonstrate how the mechanisms change as each transformation proceeds. In particular, thernsecond dehydration step of nedocromil sodium trihydrate cannot be described by any knownrnmodel. In conclusion, the model-free approach represents solid-state kinetics better than thernmodel-fitting approach.