Solubility Determination of c-Met Inhibitor in Solvent Mixtures and Mathematical Modeling to Develop Nanosuspension Formulation

Abstract

The solubility and dissolution thermodynamics of new c-Met inhibitor, ABN401, were determined in eleven solvents and Transcutol® HP–water mixture (TWM) from 298.15 to 318.15 K. The experimental solubilities were validated using five mathematical models, namely modified Apelblat, van’t Hoff, Buchowski–Ksiazaczak λh, Yalkowsky, and Jouyban–Acree van’t Hoff models. The experimental results were correlated and utilized further to investigate the feasibility of nanosuspension formation using liquid anti-solvent precipitation. Thermodynamic solubility of ABN401 increased significantly with the increase in temperature and maximum solubility was obtained with Transcutol® HP while low solubility in was obtained water. An activity coefficient study indicated that high molecular interaction was observed in ABN401–Transcutol® HP (THP). The solubility increased proportionately as the mole fraction of Transcutol® HP increased in TWM, which was also supported by a solvent effect study. The result suggested endothermic and entropy-driven dissolution. Based on the solubility, nanosuspension was designed with Transcutol® HP as solvent, and water as anti-solvent. The mean particle size of nanosuspension decreased to 43.05 nm when the mole fraction of ABN401 in THP, and mole fraction of ABN401 in TWM mixture were decreased to 0.04 and 0.1. The ultrasonicated nanosuspension appeared to give comparatively higher dissolution than micronized nanosuspension and provide a candidate formulation for in vivo purposes.

Experimental and Theoretical Screening for Green Solvents Improving Sulfamethizole Solubility

“…Therefore, by optimizing binary mixture composition, one can obtain the solvent with precise characteristics suitable for a particular technological application. This includes antisolvent crystallization techniques, which have been used to obtain a formulation with Materials 2021, 14, 5915 2 of 22 the appropriate particle size characterized by improved bioavailability [8][9][10]. Multicomponent solvents have also been applied in liquid drug formulations.…”

Thermodynamic Characteristics of Phenacetin in Solid State and Saturated Solutions in Several Neat and Binary Solvents

“…Some of the most popular models are van’t Hoff [ 14 ], Apelblat [ 15 , 16 ], Buchowski–Ksiazczak (λh) [ 17 ], Wilson [ 18 ], NRTL [ 19 ], and Jouyban–Acree [ 20 ]. These approaches became popular due to the quality of data fitting, model simplicity, and a relatively small number of variables [ 21 , 22 , 23 , 24 , 25 , 26 ]. These empirical or semi-empirical approaches offer the thermodynamic interpretation of the dissolution process in relation to the concept of an ideal solubility, which is the amount of solute capable to be dissolved by an ideal solvent, i.e., the solvent characterized by activity coefficient equal to unity [ 27 ].…”