Saieede Soltani - Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Parvin Zakeri-Milani - Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Mohammad Barzegar-Jalali - Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
Mitra Jelvehgari - Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Objective(s): Ketotifen fumarate (KF) is a selective and noncompetitive histamine antagonist (H۱-receptor) that is used topically in the treatment of allergic conditions of rhinitis and conjunctivitis. The aim of this study was to formulate and improve an ophthalmic delivery system of KF.Ocular nanoparticles were prepared with the objective of reducing the frequency of administration and obtaining controlled release to improve the anti-inflammatory drug delivery. Materials and Methods:In the present study, ocular KF loaded Eudragit RL ۱۰۰ nanoparticles were prepared using O/W solvent diffusion method. The nanoparticles were evaluated for particle size, entrapment efficiency, surface morphology, X-ray diffraction (XRD), Fourier transform spectroscopy (FTIR), and differential scanning calorimetry (DSC). In vitro release and permeation studies were also carried out on nanoparticles. Results: An average size range of ۱۸۲ to ۳۱۴.۳۰ nm in diameter was obtained and encapsulation efficiency up to ۹۵.۰% was observed for all the formulations. Drug release for all formulations after ۲۴ hr was between ۶۵.۵۱% and ۸۸.۸۲% indicating effective controlled release property of KF. The mechanism of drug release for best formulation was found to be fickian diffusion mechanism. KF nanoparticles containing high polymer concentration (۱:۱۵) presented a faster drug release and a higher drug penetration; on the contrary, nanoparticles containing low polymer concentration (۱:۷.۵) were able to give a more sustained release of the drug and thus a slower KF permeation through the cornea. Conclusion: The study revealed that KF NPs were capable of releasing the drug for a prolonged period of time and increasing the ocular bioavailability.

Eudragit RL ۱۰۰, Ketotifen fumarate, Nanoparticle, Ocular