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      Formulation Development and Evaluation of the Therapeutic Efficacy of Brinzolamide Containing Nanoemulsions

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          Abstract

          Brinzolamide (BZ) is an intraocular pressure reducing agent with low bioavailability. The purpose of the present study was to overcome this issue by development of BZ containing nanoemulsions (NEs) as an ocular drug delivery system with desirable therapeutic efficacy. Brinzolamide NEs were prepared by the spontaneous emulsification method. Based on initial release studies, twelve formulations with the slowest release characteristics were subjected to further physicochemical investigations such as particle size, polydispersity index, pH, refractive index, osmolality and viscosity. The therapeutic efficacy of these formulations was assessed by measuring the intraocular pressure after instillation of the prepared NEs in normotensive albino rabbit eyes. Nanoemulsions with suitable physicochemical properties exhibited high formulation stability under different conditions. more over biological evaluations indicated that using lower drug concentrations in NE formulations (0.4%) had a similar or even better pharmacodynamic effect compared to the commercial suspension with a higher drug concentration (1%). Our findings suggest that NEs could be effectively used as carriers for enhancing the bioavailability of topically applied ophthalmic drugs.

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          Most cited references49

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          Ocular drug delivery.

          Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases.
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            Nano-emulsions

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              Challenges and obstacles of ocular pharmacokinetics and drug delivery.

              Arto Urtti (2006)
              Modern biological research has produced increasing number of promising therapeutic possibilities for medical treatment. These include for example growth factors, monoclonal antibodies, gene knockdown methods, gene therapy, surgical transplantations and tissue engineering. Ocular application of these possibilities involves drug delivery in many forms. Ocular drug delivery is hampered by the barriers protecting the eye. This review presents an overview of the essential factors in ocular pharmacokinetics and selected pharmacological future challenges in ophthalmology.
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                Author and article information

                Journal
                Iran J Pharm Res
                Iran J Pharm Res
                IJPR
                Iranian Journal of Pharmaceutical Research : IJPR
                Shaheed Beheshti University of Medical Sciences (Tehran, Iran )
                1735-0328
                1726-6890
                Summer 2017
                : 16
                : 3
                : 847-857
                Affiliations
                [a ] Department of Pharmaceutics, School of Pharmacy & Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
                [b ] School of Applied Sciences, Auckland University of Technology, New Zealand.
                [c ] Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, University of Auckland, New Zealand.
                Author notes
                [* ]Corresponding author: E-mail: mforoutan@sbmu.ac.ir
                Article
                ijpr-16-0847
                5610741
                3ad04062-448a-4f51-8835-b5b9fadbea3c
                © 2017 by School of Pharmacy, Shaheed Beheshti University of Medical Sciences and Health Services

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : July 2016
                : August 2016
                Categories
                Original Article

                ocular drug delivery,brinzolamide,nanoemulsion,physicochemical characterization,ocular bioavailability,therapeutic efficacy

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