Evolution of the interaction of a new chemical entity, eflucimibe, with γ-cyclodextrin during kneading process

The aim of this study was to enhance the low solubility of eflucimibe, a new chemical entity which can be used as medicine to treat dyslipidemiae, by complexation with gamma-cyclodextrin. The complex was prepared using kneading method. The interaction evolution was studied during process by comparison of the semi-solid and physico-chemical states of the product. The evolution of the semi-solid state was followed by torque measurement when the evolution of physico-chemical state was studied by differential scanning calorimetry, infrared spectroscopy and by determination of the drug solubilisation profile. The interaction, which occurs during the process, is characterised by a modification of the product consistency and by a disappearance of the drug endothermic peaks, a disappearance of a drug spectral band and a widely improvement of the drug solubilisation profile. Indeed, after complete interaction, the drug quantity solubilised in specific conditions increased about 44-fold compared to those of untreated drug. Moreover, the comparison of the physico-chemical and semi-solid states during kneading process clearly shows that when the interaction takes place, a solidification of the paste occurs. The results of these works suggested that the formation of new solid phase allows an enhancement of the solubility of eflucimibe. (C) 2004 Elsevier B.V. All rights reserved.