Equilibrium solubility, solvent effect, and equation correlations of cyclosporine in twenty mono solvents and four binary mixtures

Cyclosporine (cyclosporin A, CsA) has potent immunosuppressive properties, reflecting its ability to block the transcription of cytokine genes in activated T cells. It is well established that CsA through formation of a complex with cyclophilin inhibits the phosphatase activity of calcineurin, which regulates nuclear translocation and subsequent activation of NFAT transcription factors. In addition to the calcineurin/NFAT pathway, recent studies indicate that CsA also blocks the activation of JNK and p38 signaling pathways triggered by antigen recognition, making CsA a highly specific inhibitor of T cell activation. Here we discuss the action of CsA on JNK and p38 activation pathways. We also argue the potential of CsA and its natural counterparts as pharmacological probes. Show more

The experimental conditions that affect equilibrium solubility values measured by the classical saturation shake-flask method have been examined, using hydrochlorothiazide as a model compound. Modifications in temperature, sedimentation time, composition of aqueous buffer and the technique of separation of solid and liquid phases were all found to influence the equilibrium solubility results strongly. However, variations in the amount of solid excess and stirring time were found to have less influence. In the light of these observations, a new, shorter protocol has been developed for measurements of equilibrium solubility, together with recommendations for good analytical practice. The equilibrium solubilities of five other drugs were measured to verify the new protocol. Show more