Abstract. 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.
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.
Background:
Self-assembled drug delivery systems are of much interest since they can be produced by simple
low cost and solvent-free procedures. Pharmacosomes are supramolecular-structured nanocarriers with benefits for drug
stability and targeting delivery. Amphotericin B (AmB) still remains an important agent for the treatment of invasive mold
infections, e.g invasive aspergillosis, although the challenge for new formulations is still prevailing due to high rates of
toxicity.
Objective:
We have previously reported the incorporation of AmB into 12-hydroxystearic acid lipid-based microtubes
(MTs) for topical use, herein we report the ability of AmB-MTs to self-assemble into vesicles upon dilution.
Methods:
AmB-MTs with different drug concentration (1, 3, 5 mg/ml) were prepared and size determination was carried
out for different dilutions. Morphology was evaluated by microscopy. In vitro cytotoxicity was evaluated in Vero cells and
in vitro activity against Aspergillus fumigatus and Aspergillus flavus was assessed.
Results:
AmB-MTs closed upon dilution to form vesicles ranging from 200 nm to 1µm. AmB MIC (Minimun inhibitory
concentration) for both Aspergillus species was 0.0625 and 0.125 µg/ml for dispersion and reconstituted lyophilized,
respectively.
Conclusion:
AmB pharmacosome-like vesicles are smaller structures than MTs may thus be favourable for other delivery
routes. We assume that this kind of pharmacosomes-like carrier is a promising model for the obtention of new vesicular
carriers based on lipid MTs.
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