Commercially available ocular hypotensive products: preservative concentration, stability, storage, and in-life...

With the recent addition of several new ocular hypotensive agents to the pharmacopeia, glaucomatologists have more choices in selection of pharmacotherapy. Several of these new agents have special storage requirements or a limited shelf-life when stored under certain conditions.

To better inform physicians and patients about pharmaceutical issues relating to the correct usage or storage of ophthalmic products used to manage glaucoma, the authors reviewed the US Food and Drug Administration requirements for sterile ophthalmic preparations, together with the United States Pharmacopeia 24. They also reviewed the Ophthalmic Physicians Desk Reference (2000 edition) for pharmaceutical information regarding branded glaucoma-solution products.

The US Food and Drug Administration requires that both analytical tests (e.g., concentration of preservative) and functional tests (e.g., preservative efficacy tests) be undertaken to show the sterility of liquid products. In addition, extensive chemical testing of the potency and stability of the active molecule and other physicochemical properties of the formulation are needed to justify expiration dates and determine the shelf-life of the product. Of the 19 products that met the search criteria, 17 (89%) used benzalkonium chloride as the primary preservative agent, in weight-to-volume ratios ranging from 0.004% (Betagan, Optipranolol) to 0.020% (Xalatan). Five products had a warning against freezing, and 12 required protection from light. Only one product required refrigerated storage before opening, though most products specify an upper range for temperature exposure during storage.

Physicians and their patients need to be aware of the special requirements of each product to assure that they receive the dose of medication as prescribed. The distinction between stability during storage before dispensing (shelf-life) and the acceptable "in-use life" after opening of the dispensed product are essential for the safe and efficacious management of glaucoma.