Sorption of antimicrobial agents in blow-fill-seal packs

Abstract

The present work studies the interaction of methyl paraben (MPB) and propyl paraben (PPB), two widely used antimicrobial agents in multi-dose ophthalmic formulations, with 5 mL, low density polyethylene (LDPE) and polypropylene (PP) blow-fill-seal (BFS) packs, by subjecting the systems to accelerated stability conditions of 40°C/25% RH. The effect of pH, paraben concentration, and relative humidity (RH) on the sorption loss of both the parabens was studied. Additionally, the effects of buffer species and buffer strength on MPB sorption were studied. LDPE packs showed significantly higher loss compared to PP packs which showed< 5% loss in all cases. PPB showed a significantly higher loss (40-50%) than MPB (9-16%) in LDPE. pH (3.0, 5.0, 7.0) did not have a statistically significant effect on sorption. However, concentration, humidity and buffer at pH 7 affected paraben sorption. The application of the power law suggested that the MPB followed non-Fickian diffusion while PPB showed non-Fickian to Case II diffusion in LDPE packs. In conclusion, caution should be exercised while using parabens in LDPE BFS packs because substantial losses of the antimicrobial agent during the shelf-life can compromise the preservative effectiveness against 'in-use' contamination.

Antimicrobial Preservatives for Protein and Peptide Formulations: An Overview

“…Table 11 summarizes selected incompatibility issues of preservatives with packaging material, consumables, as well as recommended containers if mentioned in the reference [12,14,24]. Benzyl Alcohol Methylcellulose Polyethylene [119,122,123] Silicone tubing [117] Slowly adsorbed by natural rubber, neoprene rubber, and butyl rubber [14] Metal and glass container [14] Polypropylene, polyvinyl chloride containers or inert containers coated with fluorinated polymers, e.g., Teflon [14,122,123] Protected from light and air [14] Chlorobutanol Polyethylene [122,123] Polyhydroxyethyl-methacrylate (used in soft contact lenses) [14] Rubber stoppers [14] Glass or polypropylene container [14,122,123] Inert container [14] m-Cresol Silicone tubing [117] "Red rubber" * [118] "White rubber" * [118] Well-closed container, protected from light and air [14] Parabens Polyethylene: adsorption increases with increasing chain length [122,123] Polyvinyl chloride [129] Silicone tubing [127] NI Glass container [14] Polypropylene container [127] Well-closed container [14] Fluoropolymer-based tubes [127]…”

“…Over the last decades, more plastic containers are used as primary packaging material as they are cheaper, shatterproof, and lighter compared to glass container [122]. However, incompatibilities with plastic containers were also observed for several preservatives [119,122,123]. Roberts et al (1979) recognized that preservatives with increased affinity to polyethylene, represented by an increased hexane-water partition coefficient, showed a greater reduction [119].…”

“…Moreover, the group of Amin analyzed the compatibility of several preservatives (commonly used in ophthalmic preparation) after storage in low density polyethylene (LDPE) blow-fill-seal packs and polypropylene (PoP) blow-fill-seal packs at 40 • C/25% relative humidity [122,123]. Despite the cost saving advantages, blow fill seal tanks have a high sorption potential, thus leading to incompatibilities with hydrophobic excipients.…”

“…In addition, Amin et al ( 2012) investigated the sorption behavior of methyl-and propylparaben in blow-fill seal packs commonly used for ophthalmic solutions [123]. The main components of blow-fill seal packs are polyolefins, including polyethylene (most commonly low-density polyethylene (LDPE)) and polypropylene (PoP).…”

“…In conclusion, Amin et al (2012) showed that the loss of parabens is increased in low density polyethylene blow-fill-seal packs compared to polypropylene, and that the loss can be impacted by formulation variables, e.g., pH, buffer strength, and concentration. They also stressed that environmental factors such as humidity could affect the sorption rate of parabens [123].…”