A Promising New Method to Estimate Drug-Polymer Solubility at Room Temperature

被引:29
|
作者
Knopp, Matthias Manne [1 ,2 ]
Gannon, Natasha [2 ]
Porsch, Ilona [2 ]
Rask, Malte Bille [1 ,3 ]
Olesen, Niels Erik [1 ]
Langguth, Peter [2 ]
Holm, Rene [1 ,3 ]
Rades, Thomas [3 ]
机构
[1] H Lundbeck & Co AS, Pharmaceut Sci & CMC Biol, DK-2500 Valby, Denmark
[2] Johannes Gutenberg Univ Mainz, Inst Pharm & Biochem, D-55128 Mainz, Germany
[3] Univ Copenhagen, Dept Pharm, DK-2100 Copenhagen, Denmark
关键词
solubility; polymers; poorly soluble drugs; Flory-Huggins; shake-flask method; amorphous solid dispersion; solubility enhancement; thermal analysis; CRYSTALLINE DRUGS; MISCIBILITY; PREDICTION; MATRICES; PVP/VA;
D O I
10.1016/j.xphs.2016.02.017
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The established methods to predict drug-polymer solubility at room temperature either rely on extrapolation over a long temperature range or are limited by the availability of a liquid analogue of the polymer. To overcome these issues, this work investigated a new methodology where the drug-polymer solubility is estimated from the solubility of the drug in a solution of the polymer at room temperature using the shake-flask method. Thus, the new polymer in solution method does not rely on temperature extrapolations and only requires the polymer and a solvent, in which the polymer is soluble, that does not affect the molecular structure of the drug and polymer relative to that in the solid state. Consequently, as this method has the potential to provide fast and precise estimates of drug-polymer solubility at room temperature, we encourage the scientific community to further investigate this principle both fundamentally and practically. (c) 2016 American Pharmacists Association((R)). Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:2621 / 2624
页数:4
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