期刊
MOLECULAR PHARMACEUTICS
卷 20, 期 5, 页码 2568-2578出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.3c00008
关键词
amorphous solid dispersion; shear modulus; glass-transition temperature; relative humidity; WLF; master curve
Amorphous solid dispersions (ASDs) are commonly used to enhance the dissolution rate of poorly soluble active pharmaceutical ingredients (APIs). However, most ASDs tend to crystallize eventually due to thermodynamic instability. The crystallization kinetics of ASDs depend on the thermodynamic driving force and molecular mobility, which are affected by factors such as drug load, temperature, and relative humidity (RH). This study focuses on viscosity as an indicator of molecular mobility in ASDs.
Amorphous solid dispersions (ASDs) are commonly used to increase the dissolution rate of poorly soluble active pharmaceutical ingredients (APIs). Unfortunately, most ASDs are thermodynamically unstable and, even though kinetically stabilized, will thus eventually crystallize. The crystallization kinetics is determined by the thermodynamic driving force and by molecular mobility, which in turn depend on the drug load, temperature, and relative humidity (RH) at which the ASDs are stored. This work focuses on viscosity as an indicator for the molecular mobility in ASDs. The viscosity and shear moduli of ASDs consisting of the polymer poly(vinylpyrrolidone-co-vinyl acetate) or hydroxypropyl methylcellulose acetate succinate and the API nifedipine or celecoxib were studied using an oscillatory rheometer. The effects of temperature, drug load, and RH on the viscosity were investigated. With the knowledge of how much water is absorbed by the polymer or ASD and thereby also the knowledge of the glass-transition temperature of the wet polymer or ASD, the viscosity of dry and wet ASDs was predicted to be in very good agreement with experimental data just based on the viscosity of neat polymers and the glass-transition temperatures of wet ASDs.
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