Ophthalmic pharmaceutical composition containing a combination of brinzolamide and brimonidine and method of preparation thereof

A process for manufacturing an aqueous ophthalmic composition comprising Brinzolamide or a pharmaceutically acceptable salt thereof, Brimonidine or a pharmaceutically acceptable salt thereof, a polyol-borate system consisting of (1) a single polyol selected from the group consisting of mannitol and propylene glycol and (2) boric acid, a carboxyvinyl polymer, tyloxapol and benzalkonium chloride in an antimicrobially effective amount, wherein the composition satisfies USP preservative efficacy requirements and wherein the composition contains only one polyol selected from the group consisting of mannitol and propylene glycol, comprising:

• adding 90% w/v of a total amount of a final solution of water for injection in a clean glass vessel;
• Adding sodium chloride and stirring until complete dissolution;
• Adding a single polyol and stirring until complete dissolution;
• Adding boric acid and stirring until complete dissolution;
• Adding Brizolamide or a pharmaceutically acceptable salt thereof and stirring until complete dissolution;
• Adding Brimonidine or a pharmaceutically acceptable salt thereof and stirring until complete dissolution;
• Adding a carboxyvinyl polymer and tyloxapol and stirring until complete dissolution;
• Adding Benzalkonium chloride and stirring until complete dissolution;
• If necessary, adjusting pH to 6.50 with HCI/NaOH;
• Adjusting solution volume with water for injection;
• Filtering the solution through a 0.2um PVDF filter;
• and
• Filling and sealing the final solution in polypropylene vials, wherein the composition has a viscosity of from 210 cps to less than 1000 cps as measured using Brookfield viscometer at 30 rpm, spindle 31.