Explanation of the crystallization rate of amorphous nifedipine and phenobarbital from their molecular mobility as measured by C-13 nuclear magnetic resonance relaxation time and the relaxation time obtained from the heatingrate dependence of the glass transition temperature

To gain further insight into the effect of molecular mobility on the crysta llization rate of amorphous drugs, the mean relaxation times of amorphous n ifedipine and phenobarbital were calculated based on the Adam-Gibbs-Vogel ( AGV) equation, using the parameters D, T-o, and T-f, derived from the heati ng rate dependence of the glass transition temperature (T-g) of the amorpho us drug; and heat capacity of the drugs in the amorphous and crystalline st ates. These relaxation times were compared with the crystallization rate of amorphous nifedipine and phenobarbital reported previously. The spin-latti ce relaxation time (T-1) and the spin-lattice relaxation time in the rotati ng frame (T-1 rho) of phenobarbital and nifedipine carbons were also determ ined. The temperature dependence of the crystallization rate of nifedipine and phenobarbital on the T-g was coincident with that of the mean relaxatio n time calculated according to the AGV equation within experimental error, indicating that the crystallization of nifedipine and phenobarbital is larg ely correlated with molecular mobility at the temperatures studied. A C-13 nuclear magnetic resonance relaxation study indicated that the molecular mo tion of nifedipine and phenobarbital in the mid-kHz frequency range became significant at temperatures higher than T-g- 20 and T-g, respectively, (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm S ci 90:798-806, 2001.