Master curves to predict relaxation and crystallization of amorphous pharmaceutical compounds

Variability in the time to crystallization is a major technical and economic hurdle in using amorphous solids in dosage forms. It is hypothesized that amorphous solids "age", and that the older they are, the more relaxed and the higher probability of crystallization. At present, there is no method that allows the "effective age" of an amorphous raw material to be assessed relative to its unrelaxed initial condition. A method has been developed that may satisfy this unmet need and provide a first step in subsequent investigation of the crystallization event. This method consists of using enthalpy relaxation versus time master curves to enable the determination of the effective age of an amorphous compound given normal excursions in storage conditions. This work shows that master curves can be prepared for different storage conditions and subsequently be used to predict the relaxation or aging behavior of amorphous compounds with expected variations in storage conditions. Furthermore, a model has been developed verifying the hypothesis that crystallization occurs from the most relaxed segment of the amorphous population via a first order reaction.