NDLI: Prediction of Glass Transition Temperature of Freeze-Dried Formulations by Molecular Dynamics Simulation

Content Provider	Springer Nature Link
Author	Yoshioka, Sumie Aso, Yukio Kojima, Shigeo
Copyright Year	2003
Abstract	Purpose. To examine whether the glass transition temperature (T$_{g}$) of freeze-dried formulations containing polymer excipients can be accurately predicted by molecular dynamics simulation using software currently available on the market. Molecular dynamics simulations were carried out for isomaltodecaose, a fragment of dextran, and α-glucose, the repeated unit of dextran, in the presence or absence of water molecules. Estimated values of T$_{g}$ were compared with experimental values obtained by differential scanning calorimetry (DSC). Methods. Isothermal-isobaric molecular dynamics simulations (NPTMD) and isothermal molecular dynamics simulations at a constant volume (NVTMD) were carried out using the software package DISCOVER (Material Studio) with the Polymer Consortium Force Field. Mean-squared displacement and radial distribution function were calculated. Results. NVTMD using the values of density obtained by NPTMD provided the diffusivity of glucose-ring oxygen and water oxygen in amorphous α-glucose and isomaltodecaose, which exhibited a discontinuity in temperature dependence due to glass transition. T$_{g}$ was estimated to be approximately 400K and 500K for pure amorphous α-glucose and isomaltodecaose, respectively, and in the presence of one water molecule per glucose unit, T$_{g}$ was 340K and 360K, respectively. Estimated T$_{g}$ values were higher than experimentally determined values because of the very fast cooling rates in the simulations. However, decreases in T$_{g}$ on hydration and increases in T$_{g}$ associated with larger fragment size could be demonstrated. Conclusions. The results indicate that molecular dynamics simulation is a useful method for investigating the effects of hydration and molecular weight on the T$_{g}$ of lyophilized formulations containing polymer excipients, although the relationship between cooling rates and T$_{g}$ must first be elucidated to predict T$_{g}$ vales observed by DSC measurement. January 16
Starting Page	873
Ending Page	878
Page Count	6
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	20
Issue Number	6
e-ISSN	1573904X
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2003-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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