Equilibrium Solubility of Acetaminophen in Ternary Mixtures as a Tool for Design of Concentrated Parenteral Medications

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2023-12-11 DOI:10.1007/s10953-023-01347-3

Asma Romdhani, Fleming Martínez, Diego A. Chiappetta, Ángeles Peña, Abolghasem Jouyban

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Abstract

The main purpose of this research was to evaluate the mass/volume percentage (%m/v) solubility of acetaminophen (ACP) in {ethanol (EtOH) (1) + propylene glycol (PG) (2) + water (3)} mixtures from 20.0 to 40.0 °C to expand the solubility database of this drug in mixed pharmaceutical solvents useful for designing high concentrated liquid products including injectable solutions. This is because ACP is an analgesic drug widely used available for oral administration as tablets or solutions. Besides, as injectable products, it is only available for perfusion in as 1 g in 100 mL (1.0%m/v). However, it is not available as 5 mL ampules for supplying doses of 500 mg. As demonstrated in this research some cosolvent mixtures allow ACP concentrations higher than 10.0%m/v, for instance the aqueous ternary mixture with 20% w/w of ethanol and 30% w/w of PG, among other possible mixtures. Flask shake method and UV–vis spectrophotometry were used for ACP solubility determinations at different temperatures. ACP solubility results are presented as Cartesian and triangular solubility profiles. ACP solubility increases with temperature arising and the cosolvent proportion in the mixtures. Maximum %m/v ACP solubility value is observed in the aqueous ethanol binary mixture of w₁ = 0.80 at all temperatures being 21.18% at 25.0 °C. All the solubility values were well correlated using the Jouyban-Acree model obtaining mean percentage deviations of 3.8% (N = 330). In this way, %m/v equilibrium solubility of ACP in {EtOH + PG + water} mixtures has been studied and correlated at several temperatures as contribution to preformulation studies of injectable homogeneous liquid pharmaceutical dosage forms.

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将对乙酰氨基酚在三元混合物中的平衡溶解度作为设计浓缩肠外药物的工具

本研究的主要目的是评估对乙酰氨基酚（ACP）在{乙醇（EtOH）（1）+丙二醇（PG）（2）+水（3）}混合物中的质量/体积百分比（%m/v）溶解度（温度范围为 20.0 至 40.0°C），以扩展该药物在混合药用溶剂中的溶解度数据库，这对设计高浓度液体产品（包括注射溶液）非常有用。这是因为 ACP 是一种镇痛药物，广泛用于口服片剂或溶液。此外，作为注射产品，它只能以 1 克兑 100 毫升（1.0%m/v）的形式灌注。不过，它还没有 5 毫升安瓿包装的 500 毫克剂量。如本研究所示，一些共溶剂混合物可使 ACP 浓度高于 10.0%m/v，例如含有 20% w/w 乙醇和 30% w/w PG 的三元水性混合物，以及其他可能的混合物。烧瓶振荡法和紫外-可见分光光度法用于测定 ACP 在不同温度下的溶解度。ACP 的溶解度结果以直角坐标和三角形溶解度曲线的形式呈现。ACP 溶解度随着温度的升高和混合物中助溶剂比例的增加而增加。在所有温度下，w1 = 0.80 的乙醇二元水混合物中的 ACP 溶解度值最大，在 25.0 °C 时为 21.18%。使用 Jouyban-Acree 模型对所有溶解度值进行了很好的相关性分析，得出的平均百分比偏差为 3.8%（N = 330）。通过这种方法，研究了 ACP 在{EtOH + PG + 水}混合物中的 %m/v 平衡溶解度，并在多个温度下进行了相关分析，为注射用均相液体药物剂型的制剂前研究做出了贡献。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.