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Sunna Johannsdottir, Johannes Kari Kristinsson, Zoltán Fülöp, Gudrun Marta Asgrimsdottir, Einar Stefansson, Thorsteinn Loftsson; Aqueous Cyclosporin A Eye Drop Formulations with Cyclodextrin Nanoparticles. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4442.
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© ARVO (1962-2015); The Authors (2016-present)
Cyclosporin A (CyA) is a lipophilic, cyclic polypeptide drug with anti-inflammatory, immunosuppressive properties. It is used in topical treatment of dry eyes and is now commercially available in oil-based surfactant containing eye drops. Surfactants can irritate the surface of the eye causing burning, itching and irritation of the conjunctiva, and oil-based drops can result in blurred vision. The aim of this study was to develop surfactant free aqueous 0.2% (w/v) CyA eye drops where the drug is present in an aqueous vehicle containing CyA/cyclodextrin (CyA/CD) nanoparticles
Phase-solubility studies of various CDs were performed. Five eye drop formulations were then prepared based on the solubility studies results. The CyA/CD aggregation in these formulations was studied using dynamic light scattering (DLS) and by solid drug fraction (SD). One formulation was selected and 3 month toxicological study in 16 rabbits was performed, where 50 μl of eye drops were administered 1 or 2 times a day in the left eye of the rabbit. The right eyes was used as a comparison (control).
The phase-solubility studies show that CDs have solubilizing effect on CyA, and the solubility increases with increasing CD concentrations in the aqueous media. αCD had the best solubilizing effect increasing the solubility of CyA to 0.2% (w/v) upon addition of 12.5% (w/v) αCD, and was therefore selected for further development. γCD was also tested further due to its superior ability to form nanoparticles and its favorable toxicological profile.Five formulations were studied, all of them contained 12.5% (w/v) of αCD and various amounts of γCD (ranging from 0 – 12.5% w/v).SD and DLS studies showed that the formulation with the highest γCD concentrations had the most uniform particle size, around 670 nm. At lower γCD concentrations the particle size tends to be larger and micro size particles often appear. Therefore the formulation with 12.5% αCD and 12.5% γCD was selected for in vivo studies. The toxicological studies including clinical slit lamp examination and histology showed that the eye drops do not irritate the eyes in rabbits
These results show that by using a mixture of αCD and γCD we were able to develop surfactant free aqueous 0.2% (w/v) CyA eye drops where the drug is present in an aqueous vehicle containing CyA/CD nanoparticles. The eye drop does not cause ocular irritation in rabbits
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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