Soltani Saieede, Zakeri-Milani Parvin, Barzegar-Jalali Mohammad, Jelvehgari Mitra
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Iran J Basic Med Sci. 2016 May;19(5):550-60.
Ketotifen fumarate (KF) is a selective and noncompetitive histamine antagonist (H1-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.
In the present study, ocular KF loaded Eudragit RL 100 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.
An average size range of 182 to 314.30 nm in diameter was obtained and encapsulation efficiency up to 95.0% was observed for all the formulations. Drug release for all formulations after 24 hr was between 65.51% and 88.82% 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 (1:15) presented a faster drug release and a higher drug penetration; on the contrary, nanoparticles containing low polymer concentration (1:7.5) were able to give a more sustained release of the drug and thus a slower KF permeation through the cornea.
The study revealed that KF NPs were capable of releasing the drug for a prolonged period of time and increasing the ocular bioavailability.
富马酸酮替芬（KF）是一种选择性非竞争性组胺拮抗剂（H1受体），用于局部治疗鼻炎和结膜炎等过敏性疾病。本研究的目的是制备并改进KF的眼部给药系统。制备眼部纳米颗粒的目的是减少给药频率并实现控释，以改善抗炎药物的递送。
在本研究中，采用水包油溶剂扩散法制备了负载眼部KF的Eudragit RL 100纳米颗粒。对纳米颗粒进行了粒径、包封率、表面形态、X射线衍射（XRD）、傅里叶变换光谱（FTIR）和差示扫描量热法（DSC）评估。还对纳米颗粒进行了体外释放和渗透研究。
所有制剂的平均粒径范围为182至314.30 nm，包封率高达95.0%。所有制剂在24小时后的药物释放率在65.51%至88.82%之间，表明KF具有有效的控释性能。最佳制剂的药物释放机制为菲克扩散机制。含有高聚合物浓度（1:15）的KF纳米颗粒呈现出更快的药物释放和更高的药物渗透率；相反，含有低聚合物浓度（1:7.5）的纳米颗粒能够使药物更持续地释放，从而使KF透过角膜的渗透率更低。
该研究表明KF纳米颗粒能够长时间释放药物并提高眼部生物利用度。
