title: Adsorption of benzalkonium chloride by filter membranes: mechanisms and effect of formulation and processing parameters.
abstract: The purpose of this study was to elucidate the mechanism(s) of adsorption of benzalkonium chloride (BAK) by filter membranes and to determine the effect of formulation and processing parameters on the adsorption of BAK. Six different sterilizing grade filter membranes were used in this study. Adsorption was monitored by passing an aqueous solution of BAK at pH 6 through a 47-mm (14.2 cm2 effective filter area) disk filter membrane and measuring the UV absorption of the filtrate with a UV micro flow cell. Hydrophobic and/or electrostatic forces were chiefly responsible for adsorption. The adsorption properties of each filter membrane could be related to its composition. Membranes that were hydrophilic and nonionic or hydrophilic and cationic adsorbed little BAK. However, membranes that were hydrophobic or anionic exhibited significant BAK adsorption. Adsorption followed the Langmuir equation and adsorptive capacities ranged from 116 to 429 micrograms/47 mm membrane (8.17-30.23 micrograms/cm2). Formulation factors studied included the concentration of BAK, the presence of a tonicity-modifying agent (sodium chloride, mannitol, glycerin), and the presence of a chelating agent (edetate disodium). The greatest increase in adsorption of BAK occurred when sodium chloride or edetate disodium was used with membranes that contained cationic sites. The effects of flow rate, temperature, autoclaving, interrupting the flow, and presaturating the filter membrane were the processing parameters studied. The rate of adsorption was inversely related to flow rate and the extent of adsorption was inversely related to temperature. Presaturation of the filter membrane with BAK was an effective method to reduce the adsorption of BAK during filtration.
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: T
authors.initials: T
authors.lastname: Bin
authors.forename: A K
authors.initials: AK
authors.lastname: Kulshreshtha
authors.forename: R
authors.initials: R
authors.lastname: al-Shakhshir
authors.forename: S L
authors.initials: SL
authors.lastname: Hem
mesh_terms: D000327:Adsorption; D001548:Benzalkonium Compounds / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D005374:Filtration; D006863:Hydrogen-Ion Concentration; D009994:Osmolar Concentration; D011310:Preservatives, Pharmaceutical / Q000737:chemistry*; D013678:Technology, Pharmaceutical
chemical_list: D001548:Benzalkonium Compounds; D011310:Preservatives, Pharmaceutical