Claudia Salerno

Study of In Vitro Drug Release and Percutaneous Absorption of Fluconazole from Topical Dosage Forms

The present study aimed to evaluate different dosage forms, emulsions, emulgels, lipogels, and thickened microemulsion-based hydrogel, as fluconazole topical delivery systems with the purpose of determining a formulation with the capacity to deliver the whole active compound and maintain it within the skin so as to be considered a useful formulation either for topical mycosis treatment or as adjuvant in a combined therapy for Cutaneous Leishmaniasis. Propylene glycol and diethyleneglycol monoethyl ether were used for each dosage form as solvent for the drug and also as penetration enhancers. In vitro drug release after application of a clinically relevant dose of each formulation was evaluated and then microemulsions and lipogels were selected for the in vitro penetration and permeation study. Membranes of mixed cellulose esters and full-thickness pig ear skin were used for the in vitro studies. Candida albicans was used to test antifungal activity. A microemulsion containing diethyleneglycol monoethyl ether was found to be the optimum formulation as it was able to deliver the whole contained dose and enhance its skin penetration. Also this microemulsion showed the best performance in the antifungal activity test compared with the one containing propylene glycol. These results are according to previous reports of the advantages of microemulsions for topical administration and they are very promising for further clinical evaluation.

Lipid-based microtubes for topical delivery of Amphotericin B

The self-assembly process is a valuable tool for constructing nano and microstructures. Microtubes (MTs) self-assembled from amphiphiles are novel promising nanomaterials as they have easy self-assembly in aqueous solutions, reproducibility and biocompatibility. The incorporation of amphotericin B (AmB) into lipid microtubes formed from 12-hydroxystearic acid (12HSA) when mixed with ethanolamine in aqueous media was investigated. MTs of several concentrations of lipid material and AmB were prepared. The structure was characterized by phase-contrast microscopy, TEM and SEM. The type of interaction was analyzed by FTIR and DSC. Stability studies were carried out at room temperature and at 4 °C. Loading efficiency of the system was found to be much higher than the drug solubility in water. MTs with 1% of 12HSA and 1 mg/ml of AmB showed to be the most stable formulation. In vitro skin penetration assay showed a flux of 18.20±3.35 μg/cm(2). Amb-loaded MTs in vitro antifungal activity was evaluated and formulation showed similar results to that of AmB deoxycholate showing that AmB retained its antifungal activity in the MTs formulation.

Pharmaceutical optimization of lipid-based dosage forms for the improvement of taste-masking, chemical stability and solubilizing capacity of phenobarbital

Abstract Microemulsions (MEs) and self-emulsifying drug delivery systems (SEEDS) containing phenobarbital (Phe) were developed to improve its chemical stability, solubilizing capacity and taste-masking in oral liquid dosage forms. Cremophor® RH40 and Labrasol® were used as surfactants for the screening of ME regions, Capmul® MCM L, Captex® 355, Imwitor® 408, Myglyol® 840 and Isopropyl myristate were the oil phases assayed; Transcutol® P, Polyethylene-glycol 400, glycerol, Propylene-glycol and ethanol the cosurfactants. Phe stability assay was carried out (20:4:20:56% and 20:4:35:41% (w/w); surfactant:oily phase:cosurfactant:water) for both surfactants; only one containing ethanol showed significant dismissing in its drug content. Solubility capacity for these selected formulations were also evaluated, an amount between 17 and 58 mg/mL of Phe could be loaded. At last, an optimized ME formulation with Cremophor® RH40 20%, Capmul® MCM L 4%, PEG 400 35% and sucralose 2% (w/w) was chosen in order to optimize taste-masking using an electronic tongue. Strawberry along with banana and tutti-frutti flavors plus mint flavor proved to be the best ones. Labrasol-based pre-concentrates were tested for (micro)emulsifying properties; all of them resulted to behave as SEDDS. In summary, a rationale experimental design conducted to an optimized ME for Phe oral pediatric administration which was able to load 5-fold times the currently used dose (4 mg/mL), with no sign of physical or chemical instability and with improved taste; SEDDS for capsule filling were also obtained. The biopharmaceutical advantages described for these dosage forms encourage furthering in vivo evaluation.

Lipid-based Microtubes: A Promising Drug Carrier

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