Correlation of annealing with chemical stability in lyophilized pharmaceutical glasses
Correlation of annealing with chemical stability in lyophilized pharmaceutical glasses
This research constitutes a thorough study of the relationship between the chemical stability, aging state and global molecular motion on the one hand, and microscopic local mobility in multi-component systems on the other hand. The objective of the present work was to determine whether annealing a glass below Tg affects its chemical stability and determine if the rate of chemical degradation couples with global relaxation times determined using calorimetery, and/or with T1 and T1rho relaxation times measured using ssNMR. Model compounds chosen for this research were lyophilized aspartame/sucrose and aspartame/trehalose (1:10 w/w) formulations. The chemical degradation was assessed at various temperatures using high-performance liquid chromatography (HPLC) to determine the impact of annealing on chemical stability. The rate constant for chemical degradation was estimated using stretched time kinetics. The results support the hypothesis that thermal history affects the molecular mobility required for structural relaxation and such effect is critical for chemical stability, that is, a stabilization effect upon annealing is observed.
amorphous, molecular mobility, lyophilization, relaxation time constant, glass, structural relaxation, nmr relaxation, coupling, local mobility
5240-5251
Luthra, Suman A.
eb6e4fd2-c867-47db-989a-45c8d6d56ac1
Hodge, Ian M.
0f76566b-4fc9-4cfd-9b30-b08786f71f89
Utz, Marcel
c84ed64c-9e89-4051-af39-d401e423891b
Pikal, Michael J.
f5e90147-e4bf-4bad-9386-6d7ceef7ee74
December 2008
Luthra, Suman A.
eb6e4fd2-c867-47db-989a-45c8d6d56ac1
Hodge, Ian M.
0f76566b-4fc9-4cfd-9b30-b08786f71f89
Utz, Marcel
c84ed64c-9e89-4051-af39-d401e423891b
Pikal, Michael J.
f5e90147-e4bf-4bad-9386-6d7ceef7ee74
Luthra, Suman A., Hodge, Ian M., Utz, Marcel and Pikal, Michael J.
(2008)
Correlation of annealing with chemical stability in lyophilized pharmaceutical glasses.
Journal of Pharmaceutical Sciences, 97 (12), .
(doi:10.1002/jps.21391).
(PMID:18481306)
Abstract
This research constitutes a thorough study of the relationship between the chemical stability, aging state and global molecular motion on the one hand, and microscopic local mobility in multi-component systems on the other hand. The objective of the present work was to determine whether annealing a glass below Tg affects its chemical stability and determine if the rate of chemical degradation couples with global relaxation times determined using calorimetery, and/or with T1 and T1rho relaxation times measured using ssNMR. Model compounds chosen for this research were lyophilized aspartame/sucrose and aspartame/trehalose (1:10 w/w) formulations. The chemical degradation was assessed at various temperatures using high-performance liquid chromatography (HPLC) to determine the impact of annealing on chemical stability. The rate constant for chemical degradation was estimated using stretched time kinetics. The results support the hypothesis that thermal history affects the molecular mobility required for structural relaxation and such effect is critical for chemical stability, that is, a stabilization effect upon annealing is observed.
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e-pub ahead of print date: 14 May 2008
Published date: December 2008
Keywords:
amorphous, molecular mobility, lyophilization, relaxation time constant, glass, structural relaxation, nmr relaxation, coupling, local mobility
Organisations:
Magnetic Resonance
Identifiers
Local EPrints ID: 354824
URI: http://eprints.soton.ac.uk/id/eprint/354824
ISSN: 0022-3549
PURE UUID: 5cfde197-6b57-42b3-9201-69deb567cff4
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Date deposited: 23 Jul 2013 12:01
Last modified: 15 Mar 2024 03:44
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Contributors
Author:
Suman A. Luthra
Author:
Ian M. Hodge
Author:
Michael J. Pikal
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