Determination of the moisture content of bromobutyl rubber stoppers as a function of processing: implications for the stability of lyophilized products.
The purpose of the present study is to apply and contrast several analytical techniques to understand the change in moisture content of 20 mm diameter bromobutyl rubber stoppers as a function of typical stopper processing conditions. Three separate methods were examined and Karl-Fischer titration and techniques based on capacitance measurements at a thin-film sensor were found to provide comparable results. Stopper moisture levels were examined in stoppers: (i) as received from the manufacturer, (ii) following steam sterilization, (iii) as a function of various drying cycles, and (iv) during simulated hold conditions prior to use. Finally, the transfer of moisture from stopper to an actual product is examined on storage and general agreement observed between stopper drying conditions and cake moisture levels.
Templeton
Allen C
AC
Pharmaceutical Analysis and Control, Merck Research Laboratories, West Point, PA 19486, USA. allen_templeton@merck.com
Placek
Jiri
J
Xu
Hui
H
Mahajan
Rajiv
R
Hunke
William A
WA
Reed
Robert A
RA
D020724:Elastomers; D005612:Freeze Drying / Q000379:methods; D006358:Hot Temperature; D004364:Pharmaceutical Preparations / Q000032:analysis; D012408:Rubber / Q000737:chemistry*; D017186:Titrimetry / Q000379:methods; D014867:Water / Q000032:analysis*
D020724:Elastomers; D004364:Pharmaceutical Preparations; D014867:Water; D012408:Rubber; C017098:butyl rubber