The effect of inert atmospheric packaging on oxidative degradation in formulated granules.
OBJECTIVE
Oxidative degradation of drug substances in pharmaceutical products is well documented and is thought to occur in many cases via autoxidative processes involving headspace molecular oxygen in the primary package. Reducing the headspace oxygen concentration inside a package could thus be an option for reducing oxidative degradation in pharmaceutical products. The purpose of this study is to examine the effect of headspace oxygen concentration and relative humidity (RH) on the oxidative degradation of a model pharmaceutical formulation.


METHODS
Model formulations, including a drug substance known to exhibit oxidative degradation, at two different drug/excipient ratios were packaged in stoppered glass vials maintained at different oxygen concentrations, (from 0% to 20.9%) and headspace relative humidities and were stored at 40 degrees C. The oxidative degradation was quantified as a function of time.


RESULTS
The results clearly show dependence of oxidative degradation on headspace oxygen concentration, relative humidity, drug loading and time.


CONCLUSIONS
The results provided insight into the effectiveness of inert atmospheric packaging (IAP) for protecting oxidation-labile products. In light of these observations, a few strategies for practically implementing inert atmosphere packaging are also presented.
Mahajan
Rajiv
R
Pharmaceutical Research & Development, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania 19486, USA. rajiv_mahajan@merck.com
Templeton
Allen
A
Harman
Amy
A
Reed
Robert A
RA
Chern
Rey T
RT
D002626:Chemistry, Pharmaceutical; D004349:Drug Packaging / Q000379:methods* / Q000592:standards; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry* / Q000592:standards
D004364:Pharmaceutical Preparations