Merck
CN

Theoretical prediction of a phase diagram for solid dispersions.

Pharmaceutical research (2014-08-29)
Bin Tian, Xiaoyan Wang, Yuanyuan Zhang, Keru Zhang, Yu Zhang, Xing Tang
ABSTRACT

To predict the temperature-composition phase diagram of solid dispersions (SDs) through theoretical approaches using cinnarizine-Soluplus(®) SD as a model system and evaluate the predicted results. A complete phase diagram of cinnarizine-Soluplus(®) SD, including the solubility curve, miscibility curve and glass transition temperature curve, was constructed on the basis of the solid-liquid equilibrium (SLE) equation, Florry-Huggins (F-H) theory and Fox equation. Cinnarizine-Soluplus(®) SDs with different drug loadings were prepared by hot melt extrusion. The extrudates and corresponding physical mixtures were analyzed to check the predicted results. The experimental data revealed a solubility of 7.9 wt% at 110°C and a miscibility level of 65 wt% at room temperature, which were both consistent with predicted values. The predicted phase diagram agrees well with the experimental results for the non-polar components which mainly interact through dispersion forces, thus facilitating the formulation design of SDs.

MATERIALS
Product Number
Brand
Product Description

Lysine hydrochloride, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
L-Lysine monohydrochloride, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
L-Lysine monohydrochloride, reagent grade, ≥98% (HPLC)
Sigma-Aldrich
L-Lysine monohydrochloride, BioUltra, ≥99.5% (AT)
Supelco
L-Lysine hydrochloride solution, 100 mM amino acid in 0.1 M HCl, analytical standard
Sigma-Aldrich
ε-Caprolactam, 99%
Supelco
L-Lysine monohydrochloride, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
L-Lysine monohydrochloride, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Supelco
ε-Caprolactam, analytical standard