DESIGN AND EVALUATION OF CONTROLLED-RELEASE OCULAR INSERTS OF BRIMONIDINE-TARTRATE AND TIMOLOL MALEATE
Keywords:Ocular inserts, Sodium alginate, Glaucoma, in-vitro study, Timolol tartrate, Brimonidine maleate
Objective: The current work was attempted to formulate and evaluate a controlled-release matrix-type ocular inserts containing a combination of brimonidine tartrate and timolol maleate, with a view to sustain the drug release in the cul-de-sac of the eye.
Methods: Initially, the infrared studies were done to determine the drugâ€“polymer interactions. Sodium alginate-loaded ocuserts were prepared by solvent casting technique. Varying the concentrations of polymerâ€”sodium alginate, plasticizerâ€”glycerine, and cross-linking agentâ€”calcium chloride by keeping the drug concentration constant, made a total of nine formulations. These formulations were evaluated for its appearance, drug content, weight uniformity, thickness uniformity, percentage moisture loss, percentage moisture absorption, and in vitro release profile of the ocuserts. Finally, accelerated stability studies and the release kinetics were performed on the optimised formulation.
Results: It was perceived that polymer, plasticizer, and calcium chloride had a significant influence on the drug release. The data obtained from the formulations showed that formulationâ€”F9 was the optimised formulation, which exhibited better drug release. The release data of the optimised formulation tested on the kinetic models revealed that it exhibited first-order release kinetics.
Conclusion: It can be concluded that a natural bioadhesive hydrophilic polymer such as sodium alginate can be used as a film former to load water soluble and hydrophilic drugs like brimonidine tartrate and timolol maleate. Among all formulations, F9 with 400 mg sodium alginate, 2% calcium chloride and 60 mg glycerin were found to be the most suitable insert in terms of appearance, ease of handling, thickness, in vitro drug release and stability.
Mundada AS, Shrikhande BK. Design and evaluation of soluble ocular drug insert for controlled release of ciprofloxacin hydrochloride. Drug Dev Ind Pharm 2006;32:443-8.
Khurana G, Arora S, Pawar PK. Ocular insert for sustained delivery of gatifloxacin sesquihydrate: preparation and evaluations. Int J Pharm Invest 2012;2:70-7.
Shafie MAA, Rady MAH. In vitro and in vivo evaluation of timolol maleate ocular inserts using different polymers. J Clin Exp Ophthalmol 2012;3:246.
Kaul S, Kumar G, Kothiyal P. Design and evaluation of soluble ocular drug insert for controlled release of Acyclovir. Int J Drug Res Technol 2012;2:393-8.
Nair RV, Nair SC. KRA current trends in ocular drug delivery systems and its applications. Res J Pharm Technol 2015;8. Doi:10.5958/0974-360X.2015.00101.8
Parmar RB, Tank DHM. Design formulation and evaluation of reservoir type controlled released moxifloxacin hydrochloride ocular insert. Asian J Res Pharm Sci 2013;3:19-24
Himmelstein KJ, Guvenir I, Patton TF. Preliminary pharmacokinetic model of pilocarpine uptake and distribution in the eye. J Pharm Sci 1978;67:603-6.
Sachdeva D, Bhandari A. Design, formulation, evaluation of levobunolol HCl ocular inserts. J Pharm Sci Res 2011;3:1625-31.
Gupta SK, Niranjan DG, Agrawal SS, Srivastava S, Saxena R. Recent advances in the pharmacotherapy of glaucoma. Indian J Pharmacol 2008;40:197-208.
Rathore KS, Nema DRK, Sisodia DSS. Preparation and characterization of timolol maleate ocular films. Int J PharmTech Res 2010;2:995-2000.
Gupta S, gilhotra RM. Enhancement of antiglaucoma potential by novel ocular drug delivery system. Int J Pharm Pharm Sci 2011;3:55-8.
Amar A, Ashish K, Ajaykumar P, Anand J. Formulation and evaluation of controlled release ocular inserts of betaxolol hydrochloride. IOSR J Pharm 2012;2:34-8.
Shaikh HK, Kshirsagar RV, Patil SG. Mathematical models for drug release characterization: a review. World J Pharm Res 2015;4:324-38.
Carstensen T. Drug stability, Principles and practices. New York: Markel Dekker; 1989.
Chrai SS, Makoid MC, Eriksen SP, Robinson JR. Drop size and initial dosing frequency problems of topically applied ophthalmic drugs. J Pharm Sci 1974;63:333-8.
Chrai SS, Robinson JR. Ocular evaluation of methylcellulose vehicle in albino rabbits. J Pharm Sci 1974;63:1218-23.
Keister JC, Cooper ER, Missel PJ, Lang JC, Hager DF. Limits on optimizing ocular drug delivery. J Pharm Sci 1991;80:50-3.
Gurtler F, Gurny R. Patent literature review of ophthalmic inserts. Drug Dev Ind Pharm 1995;21:1-18.
Yuan J, Shang PP, Wu S. Effects of polyethene glycol on morphology, thermomechanical properties and water vapour permeability of cellulose acetate free films. Pharm Technol North Am 2001;25:62.