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Tapan Shah, Jun Inoue; Enhanced Ocular Bioavailability Of Carbonic Anhydrase Inhibitor Formulation With Novel Nanopolymers. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1975.
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The purpose of this paper is to present a novel ophthalmic composition comprising a hyperbranched polymer with carbonic anhydrase inhibitor (CAI). COSOPT® and TRUSOPT® are commercially available topical ophthalmic solutions developed for treating Glaucoma by inhibiting aqueous humor secretion. Due to poor and limited aqueous solubility of Dorzolamide at physiological pH, the pH of these commercial ophthalmic solutions (cont. 2% Dorzolamide) has to be kept at about 5.65. This low pH can lead to local eye irritation. In this study, 1.3% (w/v) CAI topical solution composition with Timolol was formulated at pH 7.0 containing 2% commercially available Polyethyleneimine hyperbranched polymer (HP) that has comparable topical availability of CAI. The main advantage is significant patient compliance because of enhanced eye comfort at pH 7.0.
The solubility of CAI (Dorzolamide and Brinzolamide) at pH 7.0 with HP at room temperature, and the stability at 40 degrees Celsius and 60 degrees Celsius for 4 weeks were determined with UPLC (Waters Acquity system, a gradient 1% Triethylamine in water: Acetonitrile method, performed at room temperature, with the flow rate of 0.7 mL/min, at 254 nm wavelength and 10 µL injection volume, was used on BEH C18 1.7 µm, 2.1x 50 mm column.). In vitro cornea permeation profile of Dorzolamide for 3 hours was evaluated by all-glass side-by-side diffusion cell study using extracted New Zealand rabbit’s cornea. A standard solution containing COSOPT® active ingredients at pH 7.0 was used as a control sample.
The solubility of CAI at pH 7.0 increased with HP dose dependently, and by at a factor of 2.5 with addition of 2% (w/v) HP to the solution. The long term stability results also indicated that the new formulation was stable without any precipitation. Consequently, the total cornea permeation rate of Dorzolamide, partition coefficient and permeability coefficient at pH 7.0 were 2.5 fold higher compared to the control sample.
A new water soluble CAI-beta blocker ophthalmic solution at pH 7.0 containing nanopolymer with comparable efficacy was discovered. The improved permeation in the presence of HP was mainly because of improved partitioning of CAI into the intact cornea epithelium.
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