Prediction of recrystallization behavior of troglitazone/polyvinylpyrrolidone solid dispersion by solid-state NMR.
The purpose of this study was to elaborate the relationship between the (13)C CP/MAS NMR spectra and the recrystallization behavior during the storage of troglitazone solid dispersions. The solid dispersions were prepared by either the solvent method or by co-grinding. The recrystallization behavior under storage conditions at 40 degrees C/94% RH was evaluated by the Kolmogorov-Johnson-Mehl-Avrami (KJMA) equation. Solid dispersions prepared by the solvent method or by prolonged grinding brought about inhibition of the nucleation and the nuclei growth at the same time. No differences in the PXRD profiles were found in the samples prepared by the co-grinding and solvent methods, however, (13)C CP/MAS NMR showed significant differences in the spectra. The correlation coefficients using partial least square regression analysis between the PXRD profiles and the apparent nuclei-growth constant or induction period to nucleation were 0.1305 or 0.6350, respectively. In contrast, those between the (13)C CP/MAS NMR spectra and the constant or the period were 0.9916 or 0.9838, respectively. The (13)C CP/MAS NMR spectra had good correlation with the recrystallization kinetic parameters evaluated by the KJMA equation. Consequently, solid-state NMR was judged to be a useful tool for the prediction of the recrystallization behavior of solid dispersions.
Ito
Atsutoshi
A
Formulation Technology Research Laboratories, Daiichi Sankyo Co, Ltd, 1-2-58, Hiromachi, Tokyo 140-8710, Japan. ito.atsutoshi.y5@daiichisankyo.co.jp
Watanabe
Tomoyuki
T
Yada
Shuichi
S
Hamaura
Takeshi
T
Nakagami
Hiroaki
H
Higashi
Kenjirou
K
Moribe
Kunikazu
K
Yamamoto
Keiji
K
D002839:Chromans / Q000032:analysis / Q000737:chemistry*; D003460:Crystallization / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D011205:Povidone / Q000032:analysis / Q000737:chemistry*; D011237:Predictive Value of Tests; D045162:Thiazolidinediones / Q000032:analysis / Q000737:chemistry*; D000077288:Troglitazone; D014961:X-Ray Diffraction / Q000379:methods
D002839:Chromans; D045162:Thiazolidinediones; D011205:Povidone; D000077288:Troglitazone