Polymers like poly(vinylpyrrolidone-co-vinyl acetate)
(PVPVA) or
hydroxypropyl methylcellulose acetate succinate (HPMCAS) are commonly
used as a matrix for amorphous solid dispersions (ASDs) to enhance
the bioavailability of the active pharmaceutical ingredients (APIs).
The stability of ASDs is strongly influenced by the water sorption
in the ASD from the surrounding air. In this work, the water sorption
in the neat polymers PVPVA and HPMCAS, in the neat API nifedipine
(NIF), and in their ASDs of different drug loads was measured above
and below the glass-transition temperature. The equilibrium water
sorption was predicted using the Perturbed-Chain Statistical Associating
Fluid Theory (PC-SAFT) combined with the Non-Equilibrium Thermodynamics
of Glassy Polymers (NET-GP).The water-sorption kinetics were modeled
using the Maxwell–Stefan approach whereas the thermodynamic
driving force was calculated using PC-SAFT and NET-GP. The water diffusion
coefficients in the polymers, NIF, or ASDs were determined using the
Free-Volume Theory. Using the water-sorption kinetics of the pure
polymers and of NIF, the water-sorption kinetics of the ASDs were
successfully predicted, thus providing the water diffusion coefficients
in the ASD as a function of relative humidity and of the water concentration
in polymers or 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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