Y. Aso et al., Feasibility of using isothermal microcalorimetry to evaluate the physical stability of amorphous nifedipine and phenobarbital, THERMOC ACT, 380(2), 2001, pp. 199-204
Feasibility of microcalorimetry to evaluate the physical stability of amorp
hous drugs was studied. Amorphous forms of nifedipine and phenobarbital wer
e prepared by melting and subsequent cooling in a differential scanning cal
orimetry (DSC) sample pan, and their heats of crystallization were monitore
d by isothermal microcalorimetry. The time required for 10% of the amorphou
s drug to crystallize (t(90)), a direct measure of the crystallization rate
, could be obtained from a single microcalorimetric trace of the amorphous
nifedipine or phenobarbital. The t(90) values were also determined by conve
ntional storage studies in which the heat of crystallization was determined
by DSC. The t(90) values obtained by microcalorimetry were consistent with
those obtained by DSC, within experimental error, indicating that microcal
orimetry is a useful method for evaluating the physical stability of amorph
ous drugs. (C) 2001 Elsevier Science B.V. All rights reserved.