Thermal characterization of the antiviral drug UC-781 and stability of its glass

Abstract

Thermal analysis was performed on the antiviral drug UC-781, both in the crystalline and in the amorphous state using differential scanning calorimetry. Characteristic temperature parameters and kinetic parameters of crystallization were determined to assess the stability of the formed glass. Cooling of liquid UC-781 at low rate resulted into recrystallization of the drug during cooling; an amorphous product could be obtained if the cooling rate was at least 90 K min −1. The T g of this product amounted to 265.6 K when the applied heating rate was 5 K min −1. The products formed at low cooling rate changed in color and texture as a result of degradation. Reheating of amorphous UC-781 through its glass transition showed two exothermic peaks whose onset and peak temperatures increased as the initial cooling rate decreased. The onset and peak temperatures of remelting of recrystallized UC-781 as well as its enthalpy of fusion generally decreased when the initial cooling rate was reduced. UC-781 glass displayed a higher stability at higher heating rates. The apparent glass transition temperature was dependent on the heating rate, and it was shown that simple first order kinetics could be used to describe the transfer from the glassy to the supercooled liquid state. The data presented in this paper indicate that both kinetic parameters of crystallization ( k), and characteristic temperature parameters can be applied to assess the stability of pharmaceutical compounds which are prone to crystallization.