The overall crystallization rates and mean relaxation times of amorphous nifedipine and phenobarbital in the presence of poly(vinylpyrrolidone) (PVP) were determined at various temperatures to gain further insight into the effect of molecular mobility on the crystallization rates of amorphous drugs
Correlation between molecular mobility and crystal growth of amorphous phenobarbital and phenobarbital with polyvinylpyrrolidone and L-proline
โ Scribed by Ossi Korhonen; Chandan Bhugra; Michael J. Pikal
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 177 KB
- Volume
- 97
- Category
- Article
- ISSN
- 0022-3549
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โฆ Synopsis
The aim of the present study is to determine if the correlation between molecular mobility and crystallization growth rates exists over a broad temperature range from temperatures below the glass transition (T(g)) to temperatures above the glass transition. Phenobarbital and solid dispersions of phenobarbital with PVP and L-proline were studied in this research. Relaxation times below and above the T(g) were measured. Crystallization was followed in a hot-stage microscope and crystal growth rates were measured by observing radial growth of a single crystal. Arrhenius type temperature dependences were found both in relaxation times and crystal growth rates over studied temperature ranges, in all cases studied except in the case of pure phenobarbital, where a change of slope was observed for the crystal growth rate for the temperature range below T(g). For all cases, molecular mobility was correlated with crystal growth rate, for the temperature range studied, with a coupling coefficient of 0.38 for phenobarbital, and 0.23 and 0.28 for solid dispersions with PVP and proline respectively. By establishing the coupling between molecular mobility and crystal growth rate, predictive models can be created to estimate the stability of amorphous materials both, for pure form as well as for solid dispersions.
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Isothermal crystallization of amorphous nifedipine, phenobarbital, and flopropione was studied at temperatures above and below their glass transition temperatures (T g ). A sharp decrease in the crystallization rate with decreasing temperature was observed for phenobarbital and flopropione, such tha
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 AdamยฑGibbsยฑVogel (AGV) equation, using the parameters D, T 0 , and T f , derived from the hea
Stability of the amorphous state has been linked to molecular mobility of the matrix; however different techniques may capture different mobility substates. Our previous work suggested that two calorimetric techniques, Isothermal Microcalorimetry (TAM) and MDSC, measured different aspects of mobilit