molecules Article Solubility Determination of c-Met Inhibitor in Solvent Mixtures and Mathematical Modeling to Develop Nanosuspension Formulation Maharjan Ravi 1 , Tripathi Julu 1, Nam Ah Kim 1,2,*, Kyeung Eui Park 2 and Seong Hoon Jeong 1,* 1 BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University, Gyeonggi 10326, Korea;
[email protected] (M.R.);
[email protected] (T.J.) 2 R&D Center, ABION Inc., Seoul 08394, Korea;
[email protected] * Correspondence:
[email protected] (N.A.K.);
[email protected] (S.H.J.); Tel.: +82-31-961-5225 (S.H.J.) 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 lh, Yalkowsky, and Jouyban–Acree van’t Hoff models. The experimental results were correlated and utilized further to investigate the feasibility of nanosus- pension 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 Citation: Ravi, M.; Julu, T.; Kim, dissolution. Based on the solubility, nanosuspension was designed with Transcutol® HP as solvent, N.A.; Park, K.E.; Jeong, S.H.