Solubility and thermodynamic function of a new anticancer drug ibrutinib in 2-(2-ethoxyethoxy)ethanol + water mixtures at different temperatures
, Faiyaz Shakeel, Mounir M. Salem-Bekhit, Muzaffar Iqbal, Nazrul Haq . 2015
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 (2.67 102 at T = 298.15 K) and
lowest in pure water (1.43 107 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.
