Sorption of benzalkonium chloride to various filters used in processing ophthalmics

Benzalkonium chloride is widely used as a preservative in ophthalmic formulations. The United Stated Pharmacopeia XXIII/National Formulary 18 states that "sterile membrane filtration under aseptic conditions is the preferred method" for sterilization of ophthalmic products, and sorption of benzalkonium chloride to filters has presented a problem in ophthalmic processing. The purpose of this study was to determine the extent of, and factors affecting, benzalkonium chloride sorption to filters. An aqueous solution of benzalkonium chloride 0.2 mg/mL was passed through syringe filters of various sizes, filter membrane media and manufacturers. The filters were of four sizes: 13- or 25-mm diameter with 0.2- or 0.45-micrometer pores. The filter membrane media were nylon, polyvinylidene fluoride (PVDF), polyethersulfone (PES) or polytetrafluoroethylene (PTFE) manufactured by Gelman Sciences or Micron Separations, Inc. A total volume of 3.6 mL in 0.6-mL increments was filtered, followed by a 1.8-mL water rinse. Samples were then analyzed by high-performance liquid chromatography. The results showed a significant difference in sorption based on all three variables. The 13-mm diameter filters absorbed less drug than the 25-mm filters, and filters with 0.45-micrometer pores adsorbed less drug than those with 0.2-micrometer pores because of smaller surface area exposed. The following sorption pattern was observed for the filter media: PVDF greater than PTFE greater than nylon greater than PES, with Micron Separations nylon filters showing a higher degree of sorption than Gelman Sciences nylon filters. The appropriate filter media and size should be chosen for ophthalmic product filtration to minimize loss of benzalkonium chloride in processing ophthalmic products.