Abstract
The container-closure system of a finished drug formulation usually contains packaging components such as glass bottles, foil laminate overwraps, and inks. These packaging materials contain a number of chemicals used during their manufacture such as organic solvents, plasticizers, and adhesives, which may be in direct or indirect contact with the drug product. Therefore, these chemical entities must be monitored and regulated to ensure that the drug's efficacy is not compromised. The goal of this study is to determine the potential volatile organic leachable compounds associated with the manufacture of foil laminate overwraps and inks that may be present in drug formulations. Past trends have been to use liquid injection or headspace injection coupled with gas chromatography for the quantification of leachable organic volatile compounds. However, these sampling techniques are futile for the low-level analysis (1 part per trillion-I 00 parts per million) of the leachable compounds due to sensitivity and reproducibility issues. In this study, a direct immersion solid phase microextraction-gas chromatographic method (SPME-GC) was developed and validated for the determination of 11 organic volatile compounds that may leach from pre-printed foil laminate overwraps into aqueous pharmaceutical formulations. The target compounds included : ethanol, acetone, isopropyl alcohol, ethyl acetate, 2-butanone, n-heptane, isopropyl acetate, n-propyl acetate, toluene, diacetone alcohol and 1-propoxy-2-propanol. Compounds were extracted from aqueous sample solutions by SPME using a 100-μm PDMS fiber, desorbed inside a GC inlet port and analyzed using a DB-1701 column. The variables affecting the SPME process such as extraction and desorption conditions were optimized. The average recoveries for all the analytes varied from 85.7% to 120.0% with the exception of n-heptane and toluene. The average recoveries for n-heptane and toluene ranged from 72.5% to 100.00% presumably due to their poor solubility in the aqueous sample matrix. The standard curves for all the compounds were linear over the concentration range investigated with coefficient of correlations, greater than 0.96. The detection and quantitation limits ranged from 0.6 ng/mL to 1.7 μg/mL and 5 ng/mL to 4.2 μg/mL, respectively. The intra-and inter-day precision was considered adequate (%RSD less than or equal to 16%) for the low-level determination of the target analytes in the sample matrix. The method was successfully applied for the determination of target compounds from pre-printed foil laminate overwraps in selected aqueous-based pharmaceutical formulations.