Zughul M B, al-Omari M, Badwan A A
Department of Chemistry, University of Jordan, Amman, Jordan.
Pharm Dev Technol. 1998 Feb;3(1):43-53. doi: 10.3109/10837459809028478.
The aim of this study was to develop models for rigorous analysis of phase solubility diagrams, particularly the descending portion, in order to obtain individual thermodynamic complex formation and solubility product constants. Additionally, the effect of varying the initial solute concentration St, in excess of the optimal solubility Sm, on the general shape of the plateau and descending portions of the solubility diagram was investigated. The solubilities of propylpapraben (Seq) were measured against initial beta-cyclodextrin concentrations (Lt) at different temperatures and different St. Equilibrium concentrations (Leq) were also measured. The only effect observed was a broadening of the plateau region with increase in St with no discernible effect on Sm. Simultaneous rigorous analysis of the rising as well as the descending portions of the phase diagram could only be interpreted in terms of formation of two soluble complexes: SL and S2L. Rigorous analysis of the descending portion allowed the determination of individual formation constants K11 (SL) and K21 (S2L) in addition to the solubility product of the less soluble complex KS11 (SL). Thermodynamic analysis of the individual solubility of propylparaben and beta-cyclodextrin was carried out in water at different temperatures. In aqueous beta-cyclodextrin solutions, however, the solubility of propylparaben is enhanced due to the formation of both SL (delta G11(0) = -26.4 kJ/mol) and S2L (delta G21(0) = -46.4 kJ/mol) soluble complexes. Formation of the SL-complex is favored both by enthalpy (delta H11(0) = -20.7 kJ/mol) and a slight increase in entropy (delta S11(0) = 18.6 J/mol.K). Formation of S2L from SL apparently involves stronger solute-SL binding (delta H21(0) = -45.9 kJ/mol) yet is retarded by a net decrease in entropy (delta S21(0) = -86.3 J/mol.K). The solubility of the SL-complex is highly endothermic (delta HS11(0) = 55.8 kJ/mol), and although is accompanied by much randomization (delta SS11(0) = 101.8 J/mol.K), its solubility remains quite low (delta GS11(0) = 25.5 kJ/mol). Molecular mechanical modeling of propylparaben/beta-cyclodextrin interactions in water revealed that the S2L-complex formation is energetically more favored.
本研究的目的是开发用于严格分析相溶解度图的模型，特别是下降部分，以获得单个热力学络合物形成常数和溶度积常数。此外，还研究了初始溶质浓度St超过最佳溶解度Sm时，对溶解度图平台和下降部分总体形状的影响。在不同温度和不同St条件下，测定了对羟基苯甲酸丙酯（Seq）的溶解度与初始β-环糊精浓度（Lt）的关系。还测定了平衡浓度（Leq）。观察到的唯一影响是随着St的增加平台区域变宽，而对Sm没有明显影响。对相图上升和下降部分的同时严格分析只能解释为形成了两种可溶性络合物：SL和S2L。对下降部分的严格分析除了可以确定较难溶络合物KS11（SL）的溶度积外，还可以确定单个形成常数K11（SL）和K21（S2L）。在不同温度下，对水相中对羟基苯甲酸丙酯和β-环糊精的个体溶解度进行了热力学分析。然而，在β-环糊精水溶液中，由于形成了SL（ΔG11(0)= -26.4 kJ/mol）和S2L（ΔG21(0)= -46.4 kJ/mol）可溶性络合物，对羟基苯甲酸丙酯的溶解度增加。SL络合物的形成在焓（ΔH11(0)= -20.7 kJ/mol）和熵略有增加（ΔS11(0)= 18.6 J/mol·K）方面都有利。从SL形成S2L显然涉及更强的溶质-SL结合（ΔH21(0)= -45.9 kJ/mol），但由于熵的净减少（ΔS21(0)= -86.3 J/mol·K）而受到阻碍。SL络合物的溶解度是高度吸热的（ΔHS11(0)= 55.8 kJ/mol），尽管伴随着大量的无序化（ΔSS11(0)= 101.8 J/mol·K），但其溶解度仍然相当低（ΔGS11(0)= 25.5 kJ/mol）。水中对羟基苯甲酸丙酯/β-环糊精相互作用的分子力学模型表明，S2L络合物的形成在能量上更有利。
