Explanation of the Crystallization Rate of Amorphous Nifedipine and Phenobarbital from Their Molecular Mobility as Measured by 13C Nuclear Magnetic Resonance Relaxation Time and the Relaxation Time Obtained from the Heating Rate Dependence of the Glass Transition Temperature

Abstract

To gain further insight into the effect of molecular mobility on the crystallization rate of amorphous drugs, the mean relaxation times of amorphous nifedipine and phenobarbital were calculated based on the Adam–Gibbs–Vogel (AGV) equation, using the parameters D, T0, and Tf, derived from the heating rate dependence of the glass transition temperature (Tg) of the amorphous drugs and heat capacity of the drugs in the amorphous and crystalline states. These relaxation times were compared with the crystallization rate of amorphous nifedipine and phenobarbital reported previously. The spin‐lattice relaxation time (T1) and the spin‐lattice relaxation time in the rotating frame (T1ρ) of phenobarbital and nifedipine carbons were also determined. The temperature dependence of the crystallization rate of nifedipine and phenobarbital on the Tg was coincident with that of the mean relaxation time calculated according to the AGV equation within experimental error, indicating that the crystallization of nifedipine and phenobarbital is largely correlated with molecular mobility at the temperatures studied. A 13C nuclear magnetic resonance relaxation study indicated that the molecular motion of nifedipine and phenobarbital in the mid‐kHz frequency range became significant at temperatures higher than Tg−20 and Tg, respectively. © 2001 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:798–806, 2001