RÉSUMÉ
Background/Objective: The aim of the study was to prepare a nanoemulsion (NE)-enriched hydrogel of econazolenitrate (EC) for a topical broad-spectrum antimycotic application. EC is classified as a Biopharmaceutical ClassificationSystem Class IV (low permeability, low solubility) drug. Nanotechnology is one of the most important approaches toimprove drugs solubility and permeability.Methods: Depending on solubility study of EC in NE components which include oils (peppermint oil, eucalyptus oil,and olive oil), surfactants (Tween 40, Brij 35, and Ceto stearyl alcohol), and co-surfactants (Propylene glycol, PEG400, and Glycerol); peppermint oil was selected as the oil phase. Tween 40 and propylene glycol were selected asthe surfactant and co-surfactant, respectively. Deionized water was used as an aqueous phase. A phase diagram wasprepared with a 5:1 weight ratio of tween 40 to propylene glycol. One percent of EC was loaded into the selectedNE system and combined with hydrogel consisting of carbopol 934 or HPMC as gelling polymer at three differentpercentages. Evaluation and in vitro release of the product were done.Results: NE Formula (F10) which is composed of 10% w/w of each the oil and surfactant mixture was selected asoptimum NE which shows a particle size of 80.57 nm and acceptable viscosity and pH (5.65). Formula (G6) which iscomposed of NE (F10) combined with hydrogel 3.5% HPMC shows satisfactory physical properties with the completeand prolonged release over 8 hours.Conclusion: The results suggest that the prepared NE-enriched hydrogel can be considered as a promising deliverysystem for class IV antifungal drug
RÉSUMÉ
Background Econazole nitrate is not effective as an antifungal eyedrop because of its poor intraocular permeability,therefore changing the formulation of econazole nitrate to improve its intraocular permeability become a critical point in the treatment of intraocular fungal infection. Objective The present study was to observe the penetration of 0.5％ econazole nitrate nanoparticles in the corneas and aqueous humors following its topicaladministration. Methods Econazole nitrate nanoparticles were prepared by quasi-emulsion solvent diffusion.Characteristics and size of nanoparticles were examined with transmission electron microscope and laser scatteringmethod,respectively.Econazole nitrate nanoparticles drops (0.5％ )was topically administered in 27 New Zealandwhite rabbits bilaterally,and aqueous humor and corneas were obtained after the application of the eye drops for 5,15,30,45,60,90,120,180,240 minutes respectively to detect the concentration of econazole nitrate with highperformance liquid chromatography (HPLC). The pharmacokinetic parameters were calculated with 3 p97pharmacokinetic computer software.The use of the animals followed the Regulation for the Administration of AffairsConcerning Experimental Animals by State Science and Technology Commission. Results The diameter of thenanoparticles was 50 nm with the round shape and encapsulation efficiency was 96.0％.Econazole nitrate nanoparticlesat the concentration of 0.5％ could be rapidly separated with other elements by HPLC with a lowest quantitativeconcentration of 0.1 mg/L.The mean recovery rates of econazole nitrate nanoparticles were 98.09％ in cornea and 99.66％ in aqueous humor,respectively after topical administration.The peak levels of econazole nitrate nanoparticles in cornea and aqueous humor were achieved at 5 minutes after application ( cornea:40.620 μg/g± 7.756 μg/g;aqueous humor:0.504 mg/L±0.153 mg/L),and its half-life( t1/2 )in cornea and aqueous humor was 23.5 minutes and 18.6 minutes,respectively. Conclusions Econazole nitrate nanoparticles at 0.5％ concentration can remain a feasible bioavailability in ocular tissue and therapeutic level in cornea and aqueous humor.
RÉSUMÉ
OBJECTIVE:To establish the preparation process and method of quality control of econazole nitrate ear-drops.METHODS:With mixture of glycerin and 75% alcohol as solvent,econazole nitrate ear-drops was prepared and the content of econazole was determined by ultraviolet spectrophotometry.The stability,irritation and in vitro antimicrobial tests were carried out.RESULTS:There was a good linearity of calibration curve of econazole in range of 200～600?g/ml,r=0.9 999,the average recovery was 100.76%,RSD=0.82%(n=5).The in vitro antimycotic MICs of econazole nitrate in ear-drops were 2?g/ml and 4?g/ml against standard and clinically isolated strains of Candida albicans respectively.CONCLUSION:The ear-drops is simple in preparation,effective in antimycotic action,good in stability and slight in irritability,and the method of quality control is simple,rapid and accurate.