Influence of excipients on thermodynamic phase behavior of pharmaceutical/solvent systems: Molecular thermodynamic model prediction

被引:15
作者
Chen, Qiao [1 ]
Ji, Yuanhui [1 ]
Ge, Kai [1 ]
机构
[1] Southeast Univ, Sch Chem & Chem Engn, Jiangsu Prov Hitech Key Lab Biomed Res, Nanjing 211189, Peoples R China
基金
中国国家自然科学基金;
关键词
Poorly soluble API; Polymeric excipients; PC-SAFT model; Solubility prediction; Thermodynamic phase behavior; PERTURBED-CHAIN SAFT; SOLID DISPERSIONS; POLYETHYLENE-GLYCOL; CHEMICAL-STABILITY; PHYSICAL STABILITY; BINARY-MIXTURES; IONIC LIQUIDS; SOLUBILITY; ACID; EQUATION;
D O I
10.1016/j.ces.2021.116798
中图分类号
TQ [化学工业];
学科分类号
0817 ;
摘要
In this work, the influence of polymeric excipients (PEG6000, PEG400, PVPK25, and HPMCE3) on thermodynamic phase behavior of active pharmaceutical ingredients (API) (mesalazine and allopurinol) and its aqueous solution was systematically investigated through experimental measurement and thermodynamic modeling. The API/excipients formulations were prepared by ball milling, and the phase behavior was measured by differential scanning calorimetry (DSC). The results showed that the solubility of API/solvent systems were all increased with higher temperature. Meanwhile, it was found that all four excipients can solubilize mesalazine and allopurinol effectively and the solubilization performance of PVPK25 and HPMCE3 were preferable to PEG. Furthermore, the thermodynamic phase behavior of API in the excipients/water ternary system was predicted by the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT), demonstrating good accordance with the experimental results with low average relative deviations (ARDs). This work was expected to provide theoretical guidance for the screening of pharmaceutical formulation excipients. (c) 2021 Elsevier Ltd. All rights reserved.
引用
收藏
页数:11
相关论文
共 59 条
[11]   Influence of PVP molecular weight on the microwave assisted in situ amorphization of indomethacin [J].
Doreth, Maria ;
Lobmann, Korbinian ;
Priemel, Petra ;
Grohganz, Holger ;
Taylor, Robert ;
Holm, Rene ;
de Diego, Heidi Lopez ;
Rades, Thomas .
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2018, 122 :62-69
[12]   Drug Solubility in Luminal Fluids from Different Regions of the Small and Large Intestine of Humans [J].
Fadda, H. M. ;
Sousa, T. ;
Carlsson, A. S. ;
Abrahamsson, B. ;
Williams, J. C. ;
Kumar, D. ;
Basit, A. W. .
MOLECULAR PHARMACEUTICS, 2010, 7 (05) :1527-1532
[13]   Modeling copolymer systems using the perturbed-chain SAFT equation of state [J].
Gross, J ;
Spuhl, O ;
Tumakaka, F ;
Sadowski, G .
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH, 2003, 42 (06) :1266-1274
[14]   Perturbed-chain SAFT: An equation of state based on a perturbation theory for chain molecules [J].
Gross, J ;
Sadowski, G .
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH, 2001, 40 (04) :1244-1260
[15]   Improved oral absorption and chemical stability of everolimus via preparation of solid dispersion using solvent wetting technique [J].
Jang, Sun Woo ;
Kang, Myung Joo .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2014, 473 (1-2) :187-193
[16]   Modeling the density of ionic liquids with ePC-SAFT [J].
Ji, Xiaoyan ;
Held, Christoph .
FLUID PHASE EQUILIBRIA, 2016, 410 :9-22
[17]   Drug Release Kinetics and Mechanism from PLGA Formulations [J].
Ji, Yuanhui ;
Lesniak, Anna Katharina ;
Prudic, Anke ;
Paus, Raphael ;
Sadowski, Gabriele .
AICHE JOURNAL, 2016, 62 (11) :4055-4065
[18]   A Novel Approach for Analyzing the Dissolution Mechanism of Solid Dispersions [J].
Ji, Yuanhui ;
Paus, Raphael ;
Prudic, Anke ;
Luebbert, Christian ;
Sadowski, Gabriele .
PHARMACEUTICAL RESEARCH, 2015, 32 (08) :2559-2578
[19]   Rivaroxaban polymeric amorphous solid dispersions: Moisture-induced thermodynamic phase behavior and intermolecular interactions [J].
Kapourani, Afroditi ;
Vardaka, Elisavet ;
Katopodis, Konstantinos ;
Kachrimanis, Kyriakos ;
Barmpalexis, Panagiotis .
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2019, 145 :98-112
[20]   Phase equilibria in polydisperse and associating copolymer solutions:: Poly (ethene-co-(meth)acrylic acid)-monomer mixtures [J].
Kleiner, M ;
Tumakaka, F ;
Sadowski, G ;
Latz, H ;
Buback, M .
FLUID PHASE EQUILIBRIA, 2006, 241 (1-2) :113-123