title: Interaction of antimicrobial preservatives with blow-fill-seal packs: correlating sorption with solubility parameters.
abstract: The aim of this work was to study the interaction of four commonly used ophthalmic antimicrobial preservatives [benzyl alcohol (BA), chlorbutol (CBL), benzalkonium chloride (BKC), and chlorhexidine gluconate (CG)] with Blow-Fill-Seal (BFS) packs. Effect of packaging material [low-density polyethylene (LDPE), polypropylene (PP)], humidity (25% RH, 75% RH) and concentration (0.5, 1.0, 2.0 mM BA/CBL in LDPE) was studied. BKC and CG gave negligible loss (<4%) in BFS packs over a period of 3 months. BA and CBL, however, gave marked losses in LDPE (ca. 70-90%) and PP (ca. 7-25%) packs. Humidity did not have any effect on the sorption loss of any preservative. Loss of BA switched from Case II to anomalous behavior with increasing initial concentration. A two-stage sorption behavior was inherent at all concentrations. Loss of CBL followed anomalous behavior with biphasic kinetics of loss. It was concluded that all the four preservatives were appropriate for use in PP BFS packs. However, only BKC and CG were amenable to be used in LDPE BFS packs. Lastly, an empirical expression consisting of the "solubility parameter distance" and "molar volume" of preservatives was developed to correlate the preservative loss in LDPE with the physicochemical properties of the preservatives.
authors.affiliation: National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India.
authors.forename: Aeshna
authors.initials: A
authors.lastname: Amin
authors.forename: Manish
authors.initials: M
authors.lastname: Dare
authors.forename: Abhay
authors.initials: A
authors.lastname: Sangamwar
authors.forename: Arvind Kumar
authors.initials: AK
authors.lastname: Bansal
mesh_terms: D000327:Adsorption; D000890:Anti-Infective Agents / Q000737:chemistry*; D001548:Benzalkonium Compounds / Q000737:chemistry*; D019905:Benzyl Alcohol / Q000737:chemistry*; D002710:Chlorhexidine / Q000031:analogs & derivatives* / Q000737:chemistry; D002724:Chlorobutanol / Q000737:chemistry*; D004349:Drug Packaging / Q000379:methods; D006813:Humidity; D020959:Polyethylene / Q000737:chemistry; D011126:Polypropylenes / Q000737:chemistry; D011310:Preservatives, Pharmaceutical / Q000737:chemistry*; D012995:Solubility
chemical_list: D000890:Anti-Infective Agents; D001548:Benzalkonium Compounds; D011126:Polypropylenes; D011310:Preservatives, Pharmaceutical; D020959:Polyethylene; D002724:Chlorobutanol; D019905:Benzyl Alcohol; C010882:chlorhexidine gluconate; D002710:Chlorhexidine