Affiliation:
1. Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
Abstract
Cabozantinib malate (CBZM), a new anticancer medication, has been studied for its solubility and thermodynamic properties in a variety of {dimethyl sulfoxide (DMSO) + water (H2O)} mixtures at 298.2–318.2 K and 101.1 kPa. Using the shake flask technique, the solubility of CBZM was assessed and the results were correlated to the van’t Hoff, Apelblat, Buchowski–Ksiazczak λh, Yalkowsky–Roseman, Jouyban–Acree, and Jouyban–Acree-van’t Hoff models. There was a significant correlation between the experimental CBZM solubility data and all computational models, as evidenced by the error values for all computational models being less than 5.0%. Temperature and DMSO mass percentage improved the CBZM mole fraction solubility in the cosolvent solutions of {DMSO + H2O}. At 318.2 K, pure DMSO had the highest mole fraction solubility of CBZM (4.38 × 10−2), whereas pure H2O had the lowest mole fraction solubility (2.24 × 10−7 at 298.2 K). The positive values of computed thermodynamic parameters indicated that the dissolution of CBZM was endothermic and entropy-driven in all of the {DMSO + H2O} solutions investigated. It was found that the CBZM solvation in {DMSO + H2O} solutions is governed by enthalpy. When compared to CBZM-H2O, CBZM-DMSO showed the highest molecular interactions. The findings of this investigation demonstrated that DMSO has a great deal of potential for CBZM solubilization in H2O.
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
Reference53 articles.
1. Enhancing the oral absorption of kinase inhibitors using lipophilic salts and lipid-based formulations;Williams;Mol. Pharm.,2018
2. US. Department of Health and Human Services, Food and Drug Administration (FDA), and Center for Drug Evaluation and Research (CDER) (2017). Cabometyx® (Cabozantinib) Tablets, for Oral Use. Guidance for Industry, Draft guidance.
3. Protein kinases-the major drug targets of the twenty first century?;Cohen;Nat. Rev. Drug Discov.,2002
4. Tyrosine kinase inhibition: An approach to drug development;Levitzki;Science,1995
5. Targeting cancer with small molecule kinase inhibitors;Zhang;Nat. Rev. Cancer,2009
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