Abstract:
© 2019 Elsevier B.V. Formation of amorphous solid dispersions is an effective way to enhance the bioavailability of drugs. One of the main disadvantages of such systems is their low storage stability. Estimation and prognosis of storage stability of the amorphous solid dispersions are possible through modeling of the kinetics of crystallization by the Arrhenius equation and the resulting parameters, i.e., activation energy and pre-exponential factor. These parameters can be determined using the non-isothermal kinetics methods based on both model-fitting and model-free approaches using the differential scanning calorimetry data. In the present work, the formation of amorphous solid dispersions of the phenacetin model drug with polyvinylpyrrolidone of different molecular masses (3500–1.3 × 10 6 g·mol −1 ) was studied in a wide range of heating and cooling rates. The kinetic parameters of the crystallization process of the active pharmaceutic ingredient in the solid dispersions with increased drug content were determined. The dependence of the kinetic parameters of phenacetin cold crystallization on the molecular weight of the polymer is non-linear. The approaches used in the present work can find applications for the estimation of kinetic stability of amorphous pharmaceutical systems prone to crystallization.
