Relaxation Dynamics and Crystallization Study of Sildenafil in the Liquid and Glassy States

Relaxation Dynamics and Crystallization Study of Sildenafil in the Liquid and Glassy States

In this paper, the physical stability and molecular dynamics of amorphous sildenafil are investigated in both the liquid and glassy states. We have established that the amorphous sildenafil is resistant to recrystallization at temperatures below the glass transition temperature T g during the experi...

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Bibliographic Details
Published in:Molecular pharmaceutics Vol. 10; no. 6; pp. 2270 - 2282
Main Authors: Kolodziejczyk, K, Paluch, M, Grzybowska, K, Grzybowski, A, Wojnarowska, Z, Hawelek, L, Ziolo, J. D
Format: Journal Article
Language:English
Published: United States American Chemical Society 03-06-2013
Subjects:
Calorimetry, Differential Scanning
Crystallization - methods
Kinetics
Molecular Dynamics Simulation
Piperazines - chemistry
Purines - chemistry
Sildenafil Citrate
Sulfones - chemistry
X-Ray Diffraction
amorphous drug
molecular mobility
isothermal crystallization
dielectric relaxation
viagra
physical stability
sildenafil
non-isothermal crystallization
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Summary:In this paper, the physical stability and molecular dynamics of amorphous sildenafil are investigated in both the liquid and glassy states. We have established that the amorphous sildenafil is resistant to recrystallization at temperatures below the glass transition temperature T g during the experimental period of its storage (i.e., above 6 months), however, it easily undergoes cold crystallization at T > T g. To determine the crystallization mechanism, the isothermal and non-isothermal studies of the cold crystallization kinetics of the drug are performed by using the broadband dielectric spectroscopy (BDS) and the differential scanning calorimetry (DSC), respectively. The cold crystallization mechanism has been found to be similar in both the isothermal and non-isothermal cases. This mechanism has been analyzed from the point of view of the molecular mobility of sildenafil investigated in the supercooled liquid and glassy states by using the BDS measurements in the wide temperature range. This analysis has been enriched with a new approach based on a recently reported measure of dynamic heterogeneity given by a four-point dynamic susceptibility function. No tendency to recrystallization of glassy sildenafil at T < T g is also discussed in relation to molecular dynamics of sildenafil in the glassy state. The relatively small molecular mobility reflected in one secondary relaxation as well as the predicted large time scale of structural relaxation of glassy sildenafil suggests that amorphous sildenafil should not recrystallize during its long-term storage at room temperature.
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ISSN:1543-8384
1543-8392
DOI:10.1021/mp300479r