title: Crystallization kinetics of amorphous nifedipine studied by model-fitting and model-free approaches.
abstract: The crystallization of amorphous nifedipine was studied using hot-stage microscopy (HSM), powder X-ray diffractometry (PXRD), and differential scanning calorimetry (DSC). The kinetic data obtained from DSC studies under isothermal and nonisothermal conditions were examined using both model-fitting and model-free approaches. Evaluation of 16 different models showed that model A4 (Avrami-Erofeev, n = 4) to be most appropriate for crystallization in the conversion range 0.05-0.80. This choice was based on the goodness of fit, the residual plots, and the guidance provided by the model-free approach. The model-free approach indicated that the activation energy decreases slightly as the crystallization proceeds. This variation of the activation energy with the extent of conversion determines the range of conversion over which a model can be fit, and the magnitude of the activation energy helps in the selection of the best model. The model-free approach gives much better predictions than the model of best fit and allows the experimental kinetic function to be numerically evaluated. At the early stage (alpha = 0-0.6), the numerically reconstructed model is almost identical to A4, but gradually approaches A3 (Avrami-Erofeev, n = 3) as the crystallization progresses (alpha = 0.6-0.8) and deviates from both models near the end of the reaction. This behavior may be explained by the relative contributions of nucleation and crystal growth at different stages of the reaction.
authors.affiliation: College of Pharmacy, University of Minnesota, Weaver-Densford Hall, Minneapolis, Minnesota 55455-0343, USA.
authors.forename: Deliang
authors.initials: D
authors.lastname: Zhou
authors.forename: Eric A
authors.initials: EA
authors.lastname: Schmitt
authors.forename: Geoff G
authors.initials: GG
authors.lastname: Zhang
authors.forename: Devalina
authors.initials: D
authors.lastname: Law
authors.forename: Sergey
authors.initials: S
authors.lastname: Vyazovkin
authors.forename: Charles A
authors.initials: CA
authors.lastname: Wight
authors.forename: David J W
authors.initials: DJ
authors.lastname: Grant
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D018360:Crystallography, X-Ray; D007700:Kinetics; D008853:Microscopy; D008956:Models, Chemical; D009543:Nifedipine / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D014867:Water; D009543:Nifedipine