Mohammadian Esmaeil, Dashti Mina, Martinez Fleming, Jouyban Abolghasem
Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
BMC Chem. 2024 Sep 28;18(1):190. doi: 10.1186/s13065-024-01297-x.
Budesonide (BDS) a steroid-based anti-inflammatory drug widely prescribed for various diseases, has a low aqueous solubility. In this study, we investigated cosolvency approach to study the thermodynamic specifications related to the solubility of BDS at the temperature range of 293.2-313.2 K in (1-propanol + water) mixtures applying the shaking flask method. The predictive power of different mathematical models for experimental data in the cosolvency systems was evaluated. For this purpose, the linear and nonlinear mathematical equations such as van't Hoff model (as a linear model), Buchowski-Ksiazczak equation (as a non-linear), CNIBS/R-K and MRS models (as a linear model for solvent composition at an isothermal condition), modified Wilson model (as a non-linear model for isothermal condition), the Jouyban-Acree model (as a model that considers temperature and solvent composition), and Jouyban-Acree-van't Hoff model (as a model with no further input data) were studied. Also, the Williams-Amidon excess Gibbs energy model was investigated. In addition, the related apparent thermodynamics of the BDS dissolution process in the desired temperature such as Gibbs free energy, enthalpy, and entropy, were computed by the corresponding equations. Moreover, based on the inverse Kirkwood-Buff integrals, it is demonstrated that BDS is preferentially solvated by water in water-rich mixtures. The accuracy of the fitness was evaluated with mean relative deviations (MRDs%) for back-calculated molar BDS solubility data. The result showed that the maximum solubility of BDS was obtained at 0.7 mass fraction of 1-propanol at all temperatures. Thermodynamic studies demonstrated that BDS dissolution procedures were obtained as endothermic and entropy-driven in almost all cases. The overall MRDs% values for the back-computed BDS solubility in the aqueous mixture of 1-propanol based on van't Hoff model, Buchowski-Ksiazczak equation, CNIBS/R-K model, modified Wilson model, Jouyban-Acree model, Jouyban-Acree-van't Hoff model, MRS model, and Williams-Amidon excess Gibbs energy model were found 1.93%, 1.80%, 11.68%, 33.32%, 12.30%, 9.24%, 10.70%, and 6.57%, respectively.
布地奈德（BDS）是一种广泛用于治疗各种疾病的类固醇类抗炎药物，其水溶性较低。在本研究中，我们采用摇瓶法研究了共溶剂法，以考察在293.2 - 313.2 K温度范围内，BDS在（1-丙醇 + 水）混合溶剂中的溶解度相关的热力学特性。评估了共溶剂体系中不同数学模型对实验数据的预测能力。为此，研究了线性和非线性数学方程，如范特霍夫模型（作为线性模型）、布霍夫斯基 - 西亚兹扎克方程（作为非线性模型）、CNIBS/R - K和MRS模型（作为等温条件下溶剂组成的线性模型）、修正威尔逊模型（作为等温条件下的非线性模型）、乔伊班 - 阿克里模型（作为考虑温度和溶剂组成的模型）以及乔伊班 - 阿克里 - 范特霍夫模型（作为无需进一步输入数据的模型）。此外，还研究了威廉姆斯 - 阿米登过量吉布斯自由能模型。另外，通过相应方程计算了BDS在所需温度下溶解过程的相关表观热力学性质，如吉布斯自由能、焓和熵。此外，基于逆柯克伍德 - 布夫积分，证明了在富水混合物中BDS优先被水溶剂化。通过回算的BDS摩尔溶解度数据的平均相对偏差（MRDs%）评估拟合精度。结果表明，在所有温度下，当1-丙醇的质量分数为0.7时，BDS的溶解度最大。热力学研究表明，几乎在所有情况下，BDS的溶解过程都是吸热且由熵驱动的。基于范特霍夫模型、布霍夫斯基 - 西亚兹扎克方程、CNIBS/R - K模型、修正威尔逊模型、乔伊班 - 阿克里模型、乔伊班 - 阿克里 - 范特霍夫模型、MRS模型和威廉姆斯 - 阿米登过量吉布斯自由能模型回算的BDS在1-丙醇水混合溶剂中的总体MRDs%值分别为1.93%、1.80%、11.68%、33.32%、12.30%、9.24%、10.70%和6.57%。
