Thermodynamic phase behavior of API/polymer solid dispersions.

Molecular pharmaceutics (2014-05-30)
Anke Prudic, Yuanhui Ji, Gabriele Sadowski
ABSTRACT

To improve the bioavailability of poorly soluble active pharmaceutical ingredients (APIs), these materials are often integrated into a polymer matrix that acts as a carrier. The resulting mixture is called a solid dispersion. In this work, the phase behaviors of solid dispersions were investigated as a function of the API as well as of the type and molecular weight of the carrier polymer. Specifically, the solubility of artemisinin and indomethacin was measured in different poly(ethylene glycol)s (PEG 400, PEG 6000, and PEG 35000). The measured solubility data and the solubility of sulfonamides in poly(vinylpyrrolidone) (PVP) K10 and PEG 35000 were modeled using the perturbed-chain statistical associating fluid theory (PC-SAFT). The results show that PC-SAFT predictions are in a good accordance with the experimental data, and PC-SAFT can be used to predict the whole phase diagram of an API/polymer solid dispersion as a function of the kind of API and polymer and of the polymer's molecular weight. This remarkably simplifies the screening process for suitable API/polymer combinations.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Indomethacin, 98.5-100.5% (in accordance with EP)
Supelco
Indomethacin, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Indomethacin, meets USP testing specifications
USP
Indomethacin, United States Pharmacopeia (USP) Reference Standard
Indomethacin, European Pharmacopoeia (EP) Reference Standard