Acceleration of paraben sorption to polyethylene terephthalate: a freeze-thaw phenomenon.
The evaluation of preservative stability in a formulation throughout its life cycle (production, shipping, and storage) is an important part of product development and essential to ensuring that potential microbial contamination is satisfactorily controlled. This work investigates the unexpected losses of propyl and butylparaben in oral solutions packaged in polyethylene terephthalate (PET) bottles. The samples endured a temperature-cycling study that was designed to simulate extreme temperature fluctuations that could be encountered during product shipping and handling. An investigation into the preservative-package interaction indicated that the paraben preservatives precipitate as a result of the freezing process. The precipitated parabens at the bottom of the bottle dissolve as the solution warms. Without agitation of the solution, the local concentration of the parabens in the vicinity of the dissolving solids increases and is higher than in the oral solution at large. It appears that the combination of the localized high paraben concentration and increased temperature (50 degrees C) increases the kinetics of paraben sorption.
Bergquist
Paul A
PA
Pharmaceutical Development, Merck & Co, Inc., 770 Sumneytown Pike, WP78-204, West Point, PA 19486-0004, USA. paul_bergquist@merck.com
Kemp
Eric A
EA
Seburg
Randal A
RA
Zhu
Limin M
LM
D000327:Adsorption; D004349:Drug Packaging / Q000592:standards*; D004356:Drug Storage; D005615:Freezing; D006358:Hot Temperature; D010226:Parabens / Q000737:chemistry*; D011093:Polyethylene Terephthalates / Q000737:chemistry*; D011310:Preservatives, Pharmaceutical / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties
D010226:Parabens; D011093:Polyethylene Terephthalates; D011310:Preservatives, Pharmaceutical