title: The effect of inert atmospheric packaging on oxidative degradation in formulated granules.
abstract: 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.
authors.affiliation: Pharmaceutical Research & Development, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania 19486, USA. rajiv_mahajan@merck.com
authors.forename: Rajiv
authors.initials: R
authors.lastname: Mahajan
authors.forename: Allen
authors.initials: A
authors.lastname: Templeton
authors.forename: Amy
authors.initials: A
authors.lastname: Harman
authors.forename: Robert A
authors.initials: RA
authors.lastname: Reed
authors.forename: Rey T
authors.initials: RT
authors.lastname: Chern
mesh_terms: D002626:Chemistry, Pharmaceutical; D004349:Drug Packaging / Q000379:methods* / Q000592:standards; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry* / Q000592:standards
chemical_list: D004364:Pharmaceutical Preparations