A Novel Microemulsion System for Ocular Delivery of Azithromycin: Design, Characterization and Ex-Vivo Rabbit Corneal Permeability

Abstract

Background: The poor bioavailability of ophthalmic drops is mainly due to the rapid nasolacrimal drainage of the drug and very low permeability of corneal epithelium. Hence, there is an interest to find an effective system to improve drug permeability and bioavailability. Objectives: The aim of the present study was to design and characterize a novel microemulsion system as an ocular delivery system for Azithromycin and evaluate its physicochemical characteristics and rabbit corneal permeability in order to enhance the penetration of the drug. Methods: The prepared microemulsions (MEs) were assessed for their viscosity, pH, particle size, surface tension, DSC, stability, in vitro drug release, and corneal rabbit permeability. In this study, a full factorial design was employed with 3 variables at 2 levels for preparing 8 formulations and data analysis. Results:The results showed that the average droplet size of ME formulations was in the range of 6.78 to 26.65 nm while pH values were 5.1 to 5.7 and viscosity range was 115 -361 cps. Drug release profile revealed that 79.066% of the drug released in 24 hours of the experiment. The maximum and minimum percentages of drug permeated through rabbit cornea were observed in MEA-7 (12.87%) and MEA-2 (0.909%), respectively. All ME formulations with different compositions and properties significantly increased partitioning, flux, and permeability coefficient from rabbit cornea. Dapp and Papp parameters in MEA-1 and MEA-7 formulations were 0.00882 cm 2 h -1 and 2.391 cmh -1 , which were 17.65, 35.17 times higher than those of control (AZ suspension, 1%), respectively. The

Ocular delivery of ketorolac tromethamine using microemulsion as a vehicle: Design, evaluation, and transcorneal permeation

“…Specifically, pH increased in some ketorolac MEs when the amount of oil was reduced. This data is not agreement with previous studies [18]. The selected MEs samples are showed an average viscosity range of 118-245 cps.…”

“…At predetermined time intervals (0.5, 1, 2, 3, 4, 5, 6, 7, 8 and 24 h), a 1 mL sample was withdrawn from receptor chambers and then replaced immediately with an equal volume of fresh receptor fluid until to keep sink condition in the receptor chamber during studies (In the sink condition, the concentration of the drug in the receptor is less than 10% of the saturation concentration of the drug, and thus this condition is established) and analyzed using a UV spectrophotometer at 324 nm. Then, the percentages of drug release in different time intervals were plotted and behaviors were determined by fitting on various kinetic models [18].…”

Ocular Drug Delivery Barriers—Role of Nanocarriers in the Treatment of Anterior Segment Ocular Diseases

“…Microemulsions have low surface tension and high spreading coefficient, allowing for the drug to spread and mix well with the precorneal fluid. This improves the corneal contact time of drugs [ 52 ]. They can be sterilized by filtration for formulation as eye drops.…”

Novel Ocular Drug Delivery Systems: An Update on Microemulsions

“…The stability of the MEs were tested in various temperature conditions (4°C, 25°C, 37°C, and 75% -5% RH) for 6 months, indicating that the MEs were stable. 76 A W/O ME comprised Tween 80 and Span 20, isopropyl myristate, and acetate buffer loaded with Moxifloxacin was developed for bacterial keratitis treatment. In vivo antibacterial efficacy test of ideal formulation (average globule size of <40 nm) was performed on infected rabbit eye and compared to commercial eye drops.…”