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格列吡嗪在不同纯溶剂中的溶解度测定及各种溶解度参数

Solubility Measurement and Various Solubility Parameters of Glipizide in Different Neat Solvents.

作者信息

Kalam Mohd Abul, Alshamsan Aws, Alkholief Musaed, Alsarra Ibrahim A, Ali Raisuddin, Haq Nazrul, Anwer Md Khalid, Shakeel Faiyaz

机构信息

Nanobiotechnology Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.

Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.

出版信息

ACS Omega. 2020 Jan 10;5(3):1708-1716. doi: 10.1021/acsomega.9b04004. eCollection 2020 Jan 28.

Abstract

Glipizide (GLZ) is an oral hypoglycemic agent, which is a weakly aqueous soluble drug. The solubility values of GLZ in various neat solvents are scarce in the literature. Hence, the solubility of GLZ in 12 different neat solvents, namely, "water, methanol, ethanol, isopropanol (IPA), 1-butanol, 2-butanol, ethylene glycol (EG), propylene glycol (PG), poly(ethylene glycol)-400 (PEG-400), ethyl acetate (EA), dimethyl sulfoxide (DMSO), and Transcutol-HP (THP)", at " = 298.2-318.2 K" and " = 0.1 MPa" was measured. The recorded solubilities of GLZ were correlated by "van't Hoff and Apelblat models" using root-mean-square deviation (RMSD). The overall RMSD was obtained as 1.21 and 1.40% for "Apelblat and van't Hoff models", respectively. Different solubility parameters of all studied materials including drug and solvent were calculated to find the best solvent for GLZ. The solubilities of GLZ (expressed in mole fraction) have been found highest in DMSO (2.81 × 10), followed by THP, EA, 2-butanol, 1-butanol, IPA, PEG-400, ethanol, PG, methanol, EG, and water (1.98 × 10) at " = 318.2 K". All investigated solubility parameters of GLZ were recorded very close to the DMSO. "Apparent thermodynamic analysis" showed an "endothermic and entropy-driven dissolution" of GLZ in the 12 different neat solvents. The highest molecular interactions were recorded in GLZ-DMSO compared to other combinations. Overall, DMSO has been considered as the best solvent for the solubilization of GLZ.

摘要

格列吡嗪(GLZ)是一种口服降糖药,是一种水溶性较弱的药物。文献中关于GLZ在各种纯溶剂中的溶解度数据很少。因此,测定了GLZ在12种不同纯溶剂中的溶解度,这些溶剂分别是“水、甲醇、乙醇、异丙醇(IPA)、正丁醇、异丁醇、乙二醇(EG)、丙二醇(PG)、聚乙二醇-400(PEG-400)、乙酸乙酯(EA)、二甲基亚砜(DMSO)和透皮促进剂HP(THP)”,温度范围为“298.2 - 318.2 K”,压力为“0.1 MPa”。使用均方根偏差(RMSD)通过“范特霍夫和阿佩尔布拉特模型”对记录的GLZ溶解度进行关联。对于“阿佩尔布拉特模型和范特霍夫模型”,总体RMSD分别为1.21%和1.40%。计算了包括药物和溶剂在内的所有研究材料的不同溶解度参数,以找到最适合GLZ的溶剂。在“318.2 K”时,已发现GLZ在DMSO中的溶解度(以摩尔分数表示)最高(2.81×10),其次是THP、EA、异丁醇、正丁醇、IPA、PEG - 400、乙醇、PG、甲醇、EG和水(1.98×10)。GLZ所有研究的溶解度参数记录都非常接近DMSO。“表观热力学分析”表明GLZ在12种不同纯溶剂中的溶解是“吸热且由熵驱动的”。与其他组合相比,GLZ - DMSO之间的分子间相互作用最强。总体而言,DMSO被认为是增溶GLZ的最佳溶剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8199/6990636/bd3c593df8b0/ao9b04004_0004.jpg

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