期刊
JOURNAL OF CHEMICAL THERMODYNAMICS
卷 89, 期 -, 页码 159-163出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jct.2015.04.014
关键词
Apelblat model; Ibrutinib; Solubility; Thermodynamics; Van't Hoff model; Yalkowsky model
资金
- Deanship of Scientific Research at King Saud University [RGP-VPP-202]
Ibrutinib is a recently approved anticancer drug recommended for the treatment of mantle cell lymphoma and chronic lymphocytic leukemia. It has been reported as practically insoluble in water and hence it is available in the market at higher doses. Poor solubility of ibrutinib limits its development to oral solid dosage forms only. In this work, the solubilities of ibrutinib were measured in various 2-(2-ethoxyethoxy)ethanol (Carbitol) + water mixtures at T = (298.15 to 323.15) and p = 0.1 MPa. The solubility of ibrutinib was measured using an isothermal method. The thermodynamics function of ibrutinib was also studied. The measured solubilities of ibrutinib were correlated and fitted with Van't Hoff, the modified Apelblat and Yalkowsky models. The results of curve fitting of all three models showed good correlation of experimental solubilities of ibrutinib with calculated ones. The mole fraction solubility of ibrutinib was observed highest in pure 2-(2-ethoxyethoxy)ethanol (2.67.10(-2) at T = 298.15 K) and lowest in pure water (1.43.10(-7) at T = 298.15 K) at T = (298.15 to 323.15) K. Thermodynamics data of ibrutinib showed an endothermic, spontaneous and an entropy-driven dissolution behavior of ibrutinib in all 2-(2- ethoxyethoxy) ethanol + water mixtures. Based on these results, ibrutinib has been considered as practically insoluble in water and freely soluble in 2-(2- ethoxyethoxy) ethanol. Therefore, 2-(2-ethoxyethoxy) ethanol could be used as a physiologically compatible cosolvent for solubilization and stabilization of ibrutinib in an aqueous media. The solubility data of this work could be extremely useful in preformulation studies and formulation development of ibrutinib. (C) 2015 Elsevier Ltd. All rights reserved.
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