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Itraconazole (ITR) is a potent antifungal drug. However, poor aqueous solubility limits its permeation ability across the human nail plate. Therefore, in this project, ITR was converted to hydrochloride salt (ITR-HCl) to improve its solubility and to render it amenable to iontophoresis. ITR-HCl was characterized by spectroscopic methods and antifungal efficacy was evaluated in comparison to the base. In vitro and ex vivo transport studies (passive and iontophoresis) were carried out across the porcine hoof membrane and excised human cadaver toe using two different protocols; continuous delivery of drug for 24 h and pulsed delivery of drug for 3 days (8 h/day). The antifungal efficacy of ITR-HCL was comparable to ITR. Iontophoresis was found to be more effective than passive mode of delivery of ITR-HCL. In both iontophoresis as well as passive mode of delivery, the pulsed protocol resulted in more ungual and trans-ungual delivery of drug than continuous protocol. ITR-HCL could be delivered into and across the nail plate by iontophoresis. Human cadaver toe appears to be a good model to investigate the ungual delivery of drugs.

in Spain, an updated economic assessment is required. We analyzed the costeffectiveness of rosuvastatin compared to atorvastatin in the treatment of patients at moderate, high and very high cardiovascular risk (1% Systematic Coronary Risk Evaluation [SCORE]) from the Spanish National Healthcare System (NHS) perspective. METHODS: A Markov model was developed in Microsoft Excel. Four health states were defined: patients without cardiovascular event, cerebrovascular event, coronary event and death. The highest doses of each statin intensity group were compared: rosuvastatin 10mg versus atorvastatin 20mg (moderate-intensity), and rosuvastatin 20mg versus atorvastatin 80mg (high-intensity). A time horizon of 25 years and an annual cycle length were considered. Pharmacological, monitoring, and resource use costs related to cardiovascular events were included in the model. Rosuvastatin and atorvastatin efficacy in terms of c-LDL reduction were taken from the ESC/EAS 2016 European guidelines. Utility values were associated with each health state. A 3% annual discount rate was used for costs and benefits. Incremental cost-effectiveness ratios (ICER) were estimated for each comparison and SCORE risk profile (based on gender, age, total cholesterol, blood pressure and smoking habit). A willingnessto-pay threshold of V30,000/QALY was assumed. RESULTS: Overall, 426 SCORE risk profiles were evaluated: 288 moderate, 86 high and 52 very high risk. The ICERs showed that rosuvastatin 10mg was cost-effective versus atorvastatin 20mg in 35% of the moderate profiles, the ICERs remaining were above V30,000/ QALY; 98% of the high-risk profiles and 100% of the very high-risk profiles.