Probing the Effect of Drug Loading and Humidity on the Mechanical Properties of Solid Dispersions with Nanoindentation: Antiplasticization of a Polymer by a Drug Molecule

被引:22
|
作者
Lamm, Matthew S. [1 ]
Simpson, Amanda [2 ]
McNevin, Michael [1 ]
Frankenfeld, Celeste [1 ]
Nay, Richard [2 ]
Variankaval, Narayan [1 ]
机构
[1] Merck & Co Inc, Merck Res Labs, Summit, NJ 07901 USA
[2] Hysitron Inc, Nanomech Res Lab, Minneapolis, MN USA
关键词
nanoindentation; amorphous solid dispersions; copovidone; clotrimazole; antiplasticization; CRYSTAL PROPERTIES; ELASTIC-MODULUS; HECKEL ANALYSIS; BEHAVIOR; WATER; POLY(VINYLPYRROLIDONE); INDENTATION; MISCIBILITY; GLASS; CRYSTALLIZATION;
D O I
10.1021/mp3003013
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Amorphous solid dispersions of clotrimazole in the polymer Kollidon VA64 were prepared as films in concentrations from 0% to 100% in 10% by weight increments. Nanoindentation was performed on each film at 18% and 49% relative humidity to assess the effect of drug loading and humidity on the mechanical properties of the solid dispersions. Although the addition of clotrimazole to the polymer reduces the glass transition temperature of the system as measured by differential scanning calorimetry, the hardness, reduced elastic modulus, and storage modulus were found to increase to values greater than those of either pure component up to drug loadings of approximately 60% by weight. Further addition of clotrimazole to the system resulted in decreased hardness and moduli with increased drug load. Dynamic vapor sorption of the dispersions shows that the hygroscopicity of the system is reduced as clotrimazole is added to the polymer.
引用
收藏
页码:3396 / 3402
页数:7
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