Current Eye Research, Early Online, 1–9, 2013 ! Informa Healthcare USA, Inc. ISSN: 0271-3683 print / 1460-2202 online DOI: 10.3109/02713683.2013.833630 ORIGINAL ARTICLE Physicochemical and Pharmacological Investigation of Topical Ocular w/o Microemulsion of Timolol Maleate for Treatment of Glaucoma Rahul Rama Hegde 1 , Shiv Sankar Bhattacharya 1 , Anurag Verma 1 , and Amitava Ghosh 2 1 Department of Pharmaceutics, School of Pharmaceutical Sciences, IFTM University, Moradabad, Uttar Pradesh, India and 2 Department of Pharmaceutics, Bengal College of Pharmaceutical Sciences & Research, Durgapur, West Bengal, India ABSTRACT Purpose: Ocular drug delivery system always remained associated with lots of difficulties and faced issues of poor drug absorption and poor bioavailability. Timolol maleate is a nonspecific beta blocker used for reduction of elevated intraocular pressure in glaucoma. Timolol maleate is absorbed systemically and is contraindicated in asthmatic patients. This study is focused to deliver Timolol maleate by a w/o microemulsion to extend the time of reduced intraocular pressure of glaucomatous rabbit’s eye measured by using a schoetz tonometer. Methods: The microemulsion is prepared by mixing the oily components with two nonionic surfactants, drug and water, and evaluated for the physicochemical, in vitro and in vivo parameters. Results: The colloidal system demonstrates monodisperse distribution behavior and exhibits a uniform size distribution of finite width. In vitro drug release from microemulsion was found to follow Higuchi’s pattern followed by a zero-order drug release by the emulsion. Ex vivo permeation through goat cornea revealed delayed release of Timolol maleate from microemulsion as compared with its aqueous solution. A reduction in intraocular pressure is seen lasting for 12 h compared to aqueous eye drop that lasted for only 5 h. Conclusion: In vivo reduction of intraocular pressure revealed a similar efficacy for once daily dosed 0.3% Timolol maleate in microemulsion formulation compared to 0.5% concentration in both microemulsion as well as aqueous formulation. The possible outcome of dose reduction will reduce the cardiovascular side effects generally reported with Timolol maleate eye drops. Keywords: Glaucoma, ocular bioavailability, phase transition, Timolol maleate, w/o microemulsion INTRODUCTION Glaucoma is the second leading cause of blindness next to cataract. 1 In glaucoma, the retinal ganglion cells of optic nerve degenerates and if untreated then can lead to blindness. Topical administration of intraocular pressure (IOP) reducing drugs reduces the progression of glaucoma in 90% of cases. 2 The IOP reducing drugs are generally administered topically as eye drops, but studies show that more than 50% of patients fail to adhere with the topical medication leading to failure in maintaining constant reduction of IOP resulting in therapeutic ineffective- ness. 3 Achieving ocular therapeutic effectiveness coupled with the bioavailability issues always remained as an unsolved affair for the pharmaceut- ical scientists. Microemulsions are highly stabilized surfactant solutions with abysmally reduced interfacial tension between oil and water essentially due to the presence of a surfactant molecule. 4 The surfactant molecules along with the stability enhancement also add up to Correspondence: Rahul Rama Hegde, School of Pharmaceutical Sciences, IFTM University, Delhi Road, Moradabad-244 102, Uttar Pradesh, India. Tel: +91 9557500629. Fax: +91 591 2360818. E-mail: rahulhpharma@gmail.com Received 6 June 2013; revised 15 July 2013; accepted 2 August 2013; published online 25 September 2013 1 Curr Eye Res Downloaded from informahealthcare.com by 27.123.102.162 on 09/27/13. For personal use only.