Development of Conductivity Method as an Alternative to Titration for Hydrolytic Resistance Testing Used for Evaluation of Glass Vials Used in Pharmaceutical Industry.
The European Pharmacopeia surface test to analyze the hydrolytic resistance is a common industrial method to understand and ensure the quality of produced glass vials. Hydrolytic resistance is evaluated by calculating the alkalinity of water extract from autoclaved vials by titration. As an alternative to this titration technique, a conductivity technique was assessed, which directly measures the ions in the water extract. A conductivity meter with a 12 mm diameter electrode was calibrated with a 100 μS/cm conductivity standard and carryover minimized by rinsing the probe in a water beaker per analysis. The limit of quantification at 1 μS/cm was determined as having a signal-to-noise ratio of 3 compared with the water blank. The conductivity method was selective for glass-composing elements (boron, sodium, aluminum, silicon, potassium, and calcium) within the vial extract. Accuracies of spiked conductivity standard within the range of 1 to 100 μS/cm were ±7% and had linearity with coefficient of determination (R2) of ≥0.9999. Intraday precision had a relative standard deviation (RSD) (n = 5) of ≤6% for spiked conductivity standard within the range of 1 to 100 μS/cm. Interday precision had a RSD (n = 4) of ≤6% for 10 vials from three glass vial lots. Conductivity of water extracts from nine sets of seven lots of glass vials had a precise linear relationship [R2= 0.9876, RSD = 1% (n = 9)] with titration volumes of the same lots. Conductivity results in μS/cm could be converted to titration volumes in milliliters by a conversion factor of 0.0275. The simplicity, sample stability, and individual vial analysis of the conductivity technique were more advantageous than the current titration technique.
The quality of glass vials used as primary containers in the pharmaceutical industry is of concern due to recent observations of glass flake-like delamination, or lamellae, under specific storage conditions. The current European Pharmacopoeia method to assess glass vial quality utilizes acid titration of vial extract pools to determine hydrolytic resistance or alkalinity. As an alternative to the European Pharmacopoeia method, the vial extracts were analyzed for conductivity, which directly determines the level of ions that were readily extracted from the vial surfaces. Lower quality glass would have greater surface defects that lead to higher ions extracted and higher conductivity value. The conductivity method was found to be suitable to measure the ions in water extracts and showed strong correlation with alkalinity. The advantage of the conductivity method over the alkalinity method was greater ease, lower volume requirements, stability, and flexibility in analysis.
Amgen Inc., Drug Product Development, Thousand Oaks, CA, USA.
Kiyoshi
K
Fujimori
Amgen Inc., Drug Product Development, Thousand Oaks, CA, USA.
Hans
H
Lee
Amgen Inc., Drug Product Development, Thousand Oaks, CA, USA.
Joseph
J
Phillips
Amgen Inc., Drug Product Development, Thousand Oaks, CA, USA snashed@amgen.com.
Yasser
Y
Nashed-Samuel
D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000592:standards; D003217:Conductometry / Q000379:methods* / Q000592:standards; D004349:Drug Packaging / Q000592:standards*; D005898:Glass / Q000737:chemistry* / Q000592:standards; D006868:Hydrolysis; D013242:Sterilization; D013499:Surface Properties; D014867:Water / Q000737:chemistry
D014867:Water
Alkalinity; Conductivity; Delamination; Glass; Vials