Relationship to Lattice Energy and Structure

ABSTRACT: The dehydration kinetics of piroxicam monohydrate (PM) is analyzed by both model-free and model-fitting approaches. The conventional model-fitting approach assuming a fixed mechanism throughout the reaction is found to be too simplistic. The model-free approach allows for a change of mechanism and activation energy, Ea, during the course of a reaction and is therefore more realistic. The complexity of the dehydration ofPM is illustrated by the dependence of Ea on both the heating conditions, isothermal or nonisothermal, and on the fraction of conversion, a (0 a 1). Under both isothermal andnonisothermal conditions,Ea increaseswitha for 0 a 0.25, followed by an approximately constant value of Ea during further dehydration. In the constant-Ea region, isothermal dehydration follows the two-dimensional phase boundarymodel (R2), whereas nonisothermal dehydration follows a mechanism intermediate between two-and three-dimensional diffusion that cannot be described by any of the common models. Structural studies suggest that the complex hydrogen-bond pattern inPM is responsible for the observed dehydration behavior. Ab initio calculations provide an explanation for the changes in the molecular and crystal structures accompanying the reversible change in hydration state between anhydrous piroxicam Form I andPM. This work also demonstrates the utility of model-free analysis in describing complex dehydration kinetics. 2004Wiley-Liss, Inc. and theAmericanPharmacistsAssociation JPharmSci 93:3013