TY - JOUR
T1 - The role of polymer concentration on the molecular mobility and physical stability of nifedipine solid dispersions
AU - Kothari, Khushboo
AU - Ragoonanan, Vishard
AU - Suryanarayanan, Raj
PY - 2015/5/4
Y1 - 2015/5/4
N2 - We investigated the influence of polymer concentration (2.5-20% w/w) on the molecular mobility and the physical stability in solid dispersions of nifedipine (NIF) with polyvinylpyrrolidone (PVP). With an increase in polymer concentration, the α-relaxation times measured by broadband dielectric spectroscopy were longer, which reflects a decrease in molecular mobility. In the supercooled state, at a given temperature (between 55 and 75 °C), the relaxation time increased linearly as a function of polymer concentration (2.5-20% w/w). The temperature dependence of the relaxation time indicated that the fragility of the dispersion, and by extension the mechanism by which the polymer influences the relaxation time, was independent of polymer concentration. The time for NIF crystallization also increased as a function of polymer concentration. Therefore, by using molecular mobility as a predictor, a model was built to predict NIF crystallization from the dispersions in the supercooled state. The predicted crystallization times were in excellent agreement with the experimental data.
AB - We investigated the influence of polymer concentration (2.5-20% w/w) on the molecular mobility and the physical stability in solid dispersions of nifedipine (NIF) with polyvinylpyrrolidone (PVP). With an increase in polymer concentration, the α-relaxation times measured by broadband dielectric spectroscopy were longer, which reflects a decrease in molecular mobility. In the supercooled state, at a given temperature (between 55 and 75 °C), the relaxation time increased linearly as a function of polymer concentration (2.5-20% w/w). The temperature dependence of the relaxation time indicated that the fragility of the dispersion, and by extension the mechanism by which the polymer influences the relaxation time, was independent of polymer concentration. The time for NIF crystallization also increased as a function of polymer concentration. Therefore, by using molecular mobility as a predictor, a model was built to predict NIF crystallization from the dispersions in the supercooled state. The predicted crystallization times were in excellent agreement with the experimental data.
KW - X-ray powder diffractometry
KW - crystallization
KW - dielectric spectroscopy
KW - molecular mobility
KW - nifedipine
KW - polyvinylpyrrolidone (PVP)
KW - solid dispersion
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U2 - 10.1021/mp500800c
DO - 10.1021/mp500800c
M3 - Article
C2 - 25894099
AN - SCOPUS:84929160415
VL - 12
SP - 1477
EP - 1484
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
SN - 1543-8384
IS - 5
ER -