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Molecular mobility, physical stabili...

Zhou, Deliang.

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Molecular mobility, physical stability, and transformation kinetics of amorphous and hydrated pharmaceutical solids.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Molecular mobility, physical stability, and transformation kinetics of amorphous and hydrated pharmaceutical solids./
Author:	Zhou, Deliang.
Description:	270 p.
Notes:	Source: Dissertation Abstracts International, Volume: 64-01, Section: B, page: 0223.
Contained By:	Dissertation Abstracts International64-01B.
Subject:	Chemistry, Pharmaceutical. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3078035
ISBN:	0493985646

Molecular mobility, physical stability, and transformation kinetics of amorphous and hydrated pharmaceutical solids.
Zhou, Deliang.

Molecular mobility, physical stability, and transformation kinetics of amorphous and hydrated pharmaceutical solids. - 270 p.

Source: Dissertation Abstracts International, Volume: 64-01, Section: B, page: 0223.

Thesis (Ph.D.)--University of Minnesota, 2003.

Amorphous forms have been shown to improve the bioavailability of poorly water-soluble drugs. However, its intrinsic tendency to undergo crystallization imposes great challenges in the formulation of amorphous drugs. This study aims to provide a fundamental understanding of the physical instability, that is the crystallization, of amorphous pharmaceuticals in terms of configurational thermodynamic quantities and molecular mobility, as well as solid-state kinetics.

ISBN: 0493985646Subjects--Topical Terms:

550957
Chemistry, Pharmaceutical.

Molecular mobility, physical stability, and transformation kinetics of amorphous and hydrated pharmaceutical solids.
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005 20041028080309.5
008 130614s2003 eng d
020 $a 0493985646
035 $a (UnM)AAI3078035
035 $a AAI3078035
040 $a UnM $c UnM
100 1 $a Zhou, Deliang. $3 1948121
245 1 0 $a Molecular mobility, physical stability, and transformation kinetics of amorphous and hydrated pharmaceutical solids.
300 $a 270 p.
500 $a Source: Dissertation Abstracts International, Volume: 64-01, Section: B, page: 0223.
500 $a Adviser: David James W. Grant.
502 $a Thesis (Ph.D.)--University of Minnesota, 2003.
520 $a Amorphous forms have been shown to improve the bioavailability of poorly water-soluble drugs. However, its intrinsic tendency to undergo crystallization imposes great challenges in the formulation of amorphous drugs. This study aims to provide a fundamental understanding of the physical instability, that is the crystallization, of amorphous pharmaceuticals in terms of configurational thermodynamic quantities and molecular mobility, as well as solid-state kinetics.
520 $a Using five model compounds that form amorphous phases with distinct crystallization tendencies, we have shown that configurational entropy and molecular mobility are equally important in determining the crystallization tendencies of amorphous phases in the rubbery state. For spontaneous crystallization to occur, amorphous phases with high configurational entropy require high molecular mobility. As a result, greater effort is required to stability amorphous forms of small, rigid molecules than those of large, flexible molecules.
520 $a Molecular mobility in glasses is greatly influenced by annealing and decreases with annealing time. However, for both fresh and annealed glasses, the temperature dependence of molecular mobility conforms approximately to the Arrhenius equation. Ritonavir and nifedipine glasses have different annealing behavior, which explains the differences in their stability.
520 $a Amorphous griseofulvin readily crystallizes above and below Tg. Our results suggest that molecular diffusion plays an important, but not exclusive, role in determining the rate of crystallization. However, the correlation between the rate of crystallization and molecular mobility is reduced in the glassy state. This observation is explained by the higher molecular mobility in real glasses than in the ideal glasses.
520 $a Crystallization kinetics of amorphous nifedipine was treated by model-fitting and model-free approaches. Model-free analysis provides a more realistic picture of the actual process of crystallization and gives improved predictions. The model-free treatment has also been successfully applied to the analysis of the dehydration kinetics of nedocromil sodium trihydrate. Finally, we explain the model-independent activation energy derived from isothermal kinetic data and the model-dependent activation energy derived from nonisothermal kinetic data.
520 $a The knowledge gained from this thesis should provide a fundamental understanding of the physical stability of amorphous phases and their solid-state kinetics and should assist in improving the stability of pharmaceutical products.
590 $a School code: 0130.
650 4 $a Chemistry, Pharmaceutical. $3 550957
650 4 $a Health Sciences, Pharmacology. $3 1017717
690 $a 0491
690 $a 0419
710 2 0 $a University of Minnesota. $3 676231
773 0 $t Dissertation Abstracts International $g 64-01B.
790 1 0 $a Grant, David James W., $e advisor
790 $a 0130
791 $a Ph.D.
792 $a 2003
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3078035