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 Tg 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.
Elsevier Science. All rights reserved.
Keywords:
UC-781; Crystallization; Differential scanning calorimetry; Glass transition;
Temperature; Thermal stability
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