Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
Molecules. 2021 Nov 22;26(22):7052. doi: 10.3390/molecules26227052.
Between 293.2 and 313.2 K and at 0.1 MPa, the solubility of the weak base, cinnarizine (CNZ) (3), in various {Transcutol-P (TP) (1) + water (2)} combinations is reported. The Hansen solubility parameters (HSP) of CNZ and various {(TP) (1) + water (2)} mixtures free of CNZ were also predicted using HSPiP software. Five distinct cosolvency-based mathematical models were used to link the experimentally determined solubility data of CNZ. The solubility of CNZ in mole fraction was increased with elevated temperature and TP mass fraction in {(TP) (1) + water (2)} combinations. The maximum solubility of CNZ in mole fraction was achieved in neat TP (5.83 × 10 at 313.2 K) followed by the minimum in neat water (3.91 × 10 at 293.2 K). The values of mean percent deviation () were estimated as 2.27%, 5.15%, 27.76%, 1.24% and 1.52% for the "Apelblat, van't Hoff, Yalkowsky-Roseman, Jouyban-Acree, and Jouyban-Acree-van't Hoff models", respectively, indicating good correlations. The HSP value of CNZ was closed with that of neat TP, suggesting the maximum solubilization of CNZ in TP compared with neat water and other aqueous mixtures of TP and water. The outcomes of the apparent thermodynamic analysis revealed that CNZ dissolution was endothermic and entropy-driven in all of the {(TP) (1) + water (2)} systems investigated. For {(TP) (1) + water (2)} mixtures, the enthalpy-driven mechanism was determined to be the driven mechanism for CNZ solvation. TP has great potential for solubilizing the weak base, CNZ, in water, as demonstrated by these results.
在 293.2 至 313.2 K 之间和 0.1 MPa 下,报道了弱碱性药物桂利嗪(CNZ)(3)在各种{Transcutol-P(TP)(1)+水(2)}组合中的溶解度。还使用 HSPiP 软件预测了 CNZ 和各种{(TP)(1)+水(2)}混合物中无 CNZ 的 Hansen 溶解度参数(HSP)。使用了五个不同的基于共溶剂的数学模型来关联实验测定的 CNZ 溶解度数据。CNZ 在摩尔分数中的溶解度随着温度升高和 TP 在{(TP)(1)+水(2)}组合中的质量分数升高而增加。CNZ 在摩尔分数中的最大溶解度在纯 TP 中达到(5.83×10,在 313.2 K),其次是在纯水中达到最小(3.91×10,在 293.2 K)。“Apelblat、van't Hoff、Yalkowsky-Roseman、Jouyban-Acree 和 Jouyban-Acree-van't Hoff 模型”的平均百分比偏差()估计值分别为 2.27%、5.15%、27.76%、1.24%和 1.52%,表明相关性良好。CNZ 的 HSP 值与纯 TP 接近,表明与纯水和其他 TP 和水的混合水溶液相比,CNZ 在 TP 中的溶解度最大。明显的热力学分析结果表明,在所有研究的{(TP)(1)+水(2)}系统中,CNZ 的溶解是吸热和熵驱动的。对于{(TP)(1)+水(2)}混合物,确定焓驱动机制是 CNZ 溶剂化的驱动机制。这些结果表明,TP 在水中具有很大的潜力,可以增溶弱碱性药物桂利嗪(CNZ)。