Thermodynamics Research Center / ThermoML | Fluid Phase Equilibria

ABSTRACT

Capecitabine is a widely used anticancer prodrug of 5-fluorouracil, but up to the present time there is no solubility data reported other than in supercritical carbon dioxide. In this paper, by the polythermal method, the solubility data of capecitabine in fifteen pure lower alcohols and water with methanol mixture solvents were measured from 278.15 K to 323.15 K under atmospheric pressure. The results show that the solubility of capecitabine in linear lower alcohols are bigger than that in corresponding branch chain lower alcohols, and decrease with the increasing of carbons in alkyl of alcohols. Moreover, the solubility of capecitabine increases with the increasing of temperature and mole fraction of methanol in the binary solvent mixtures of water p methanol. To expand industrial application of experimental solubility data of capecitabine in recrystallization, the values measured in selected pure lower alcohols are correlated using the modified Apelblat equation, the Buchowski-Ksiazczak-pletrzyk equation, the van't Hoff equation, the Wilson model and the NRTL model; And for the binary solvent system, the modified Apelblat equation and Jouyban-Acree model are used to correlate the solubility data. By evaluating the deviations between experimental and correlated data, all the correlated data by six models used in this research show comparable precision to those attained by careful experimental measurement. Moreover, some apparent thermodynamic quantities of the dissolution processes of capecitabine in selected solvents and temperature range studied were calculated by the parametric van't Hoff equation. According to the calculation, the dissolution of capecitabine in lower alcohols and water with methanol mixture solvents is an endothermic and entropy-driven process. The solubility and apparent dissolution characteristics of capecitabine in this paper would provide basic support for industrial design and further studies.