在 298.20 °K 时，盐酸吡格列酮在乙醇、N-甲基吡咯烷酮、聚乙二醇和水混合物中的溶解度。

Solubility of pioglitazone hydrochloride in ethanol, N-methyl pyrrolidone, polyethylene glycols and water mixtures at 298.20 °K.

机构信息

Faculty of Pharmacy, Zanjan University of Medical Sciences, Zanjan.

出版信息

Daru. 2011;19(6):440-5.

PMID:23008690

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3436081/

Abstract

BACKGROUND AND THE PURPOSE OF THE STUDY

Solubility of pharmaceuticals is still a challenging subject and solubilization using cosolvents is the most common technique used in the pharmaceutical industry. The purpose of this study was reporting and modeling the experimental molar solubility of pioglitazone hydrochloride (PGZ-HCl) in binary and ternary mixtures of ethanol (EtOH), N-methyl pyrrolidone (NMP), polyethylene glycols (PEGs) 200, 400, 600 and water along with the density of saturated solutions at 298.2 °K.

METHODS

To provide a computational method, the Jouyban-Acree model was fitted to the solubilities of the binary solvents, and solubilities of the ternary solvents were back-calculated by employing the solubility data in mono-solvents. In the next step, the ternary interaction terms were added to the model and the prediction overall mean percentage deviation (MPD) of the ternary data was reduced. Also a previously proposed version of the model was used to predict the solubility of PGZ-HCl in binary and ternary mixtures employing the experimental solubility data in mono-solvents.

RESULTS

The overall MPD of the model for fitting the binary data and predicted data of ternary solvents were 2.0 % and 50.5 %, respectively. The overall MPD of the predicted solubilities in ternary solvents using the ternary interaction terms in the model was 34.2 %, and by using the proposed version of the Jouyban-Acree model for binary and ternary data the overall correlation and prediction errors were 18.0 and 15.0 %, respectively.

CONCLUSION

The solubility of PGZ-HCl was increased by addition of EtOH, NMP, PEGs 200, 400 and 600 to aqueous solutions. The reported data extended the available solubility data of pharmaceuticals which are crucial in formulation of liquid dosage forms. The constants of the Jouyban-Acree model using the generated data are also reported which provides the possibility of solubility prediction in other solvent mixtures and temperatures.

摘要

背景与研究目的

药物的溶解度仍然是一个具有挑战性的课题，而使用助溶剂进行增溶是制药行业最常用的技术。本研究的目的是报告和建模吡格列酮盐酸盐（PGZ-HCl）在乙醇（EtOH）、N-甲基吡咯烷酮（NMP）、聚乙二醇（PEG）200、400、600 与水的二元和三元混合物以及在 298.2 K 时饱和溶液的密度的实验摩尔溶解度。

方法

为提供一种计算方法，将 Jouyban-Acree 模型拟合到二元溶剂的溶解度中，并通过使用单溶剂中的溶解度数据来反推三元溶剂的溶解度。在下一步中，向模型中添加三元相互作用项，从而降低三元数据的预测总体平均百分比偏差（MPD）。还使用了模型的一个先前提出的版本，通过使用单溶剂中的实验溶解度数据来预测 PGZ-HCl 在二元和三元混合物中的溶解度。