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

Autor: Tripathi Julu, Kyeung Eui Park, Maharjan Ravi, Nam Ah Kim, Seong Hoon Jeong
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Activity coefficient
Pharmaceutical Science
chemical and pharmacologic phenomena
02 engineering and technology
precipitation
010402 general chemistry
Mole fraction
01 natural sciences
Article
Analytical Chemistry
lcsh:QD241-441
thermodynamics
lcsh:Organic chemistry
immune system diseases
hemic and lymphatic diseases
Drug Discovery
Humans
Physical and Theoretical Chemistry
Solubility
Dissolution
Protein Kinase Inhibitors
nanosuspension
transcutol® HP
Molecular Structure
Precipitation (chemistry)
Chemistry
solubility
Organic Chemistry
hemic and immune systems
Proto-Oncogene Proteins c-met
021001 nanoscience & nanotechnology
0104 chemical sciences
Solvent
Models
Chemical
Chemistry (miscellaneous)
Solvents
Molecular Medicine
Nanoparticles
Particle size
Solvent effects
0210 nano-technology
mathematical models
Nuclear chemistry
Zdroj: Molecules, Vol 26, Iss 390, p 390 (2021)
Molecules
Volume 26
Issue 2
ISSN: 1420-3049
Popis: The solubility and dissolution thermodynamics of new c-Met inhibitor, ABN401, were determined in eleven solvents and Transcutol®
HP&ndash
water mixture (TWM) from 298.15 to 318.15 K. The experimental solubilities were validated using five mathematical models, namely modified Apelblat, van&rsquo
t Hoff, Buchowski&ndash
Ksiazaczak &lambda
h, Yalkowsky, and Jouyban&ndash
Acree van&rsquo
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&ndash
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.
Databáze: OpenAIRE
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