An investigation into the leaching of volatiles from a container closure system into ophthalmic solutions

Abstract

In this study, two separate methods were developed and validated for two different products to track three leachables; cyclohexanone, propylene glycol monoethyl ether acetate (PGMEEA), and propylene glycol monomethyl ether acetate (PGMMEA). These leachables were recently discovered to be leaching from an ink that is applied during labelling to a plastic vial containing the sample, a process known as tampoprinting. Due to the volatile nature of these leachables the best technique of tracking them is by gas chromatography (GC). This analytical separation technique utilises a system that vaporises liquid samples containing organic compounds of interest. The sample travels through a column where the sample components are separated and then detected producing a quantitative measurement of each component. In chapter 2, a direct injection gas chromatography method was developed for Product Z to track the three leachables of interest. The method was then fully validated in accordance with the current United States Pharmacopeia (USP) Category II for leachables and in line with all requirements under International Conference on Harmonisation (ICH) Q2 (R1). In chapter 3, direct injection gas chromatography could not be utilised for Product X due to the different nature of its sample matrix to Product Z. Instead, a method to track the Tampoprint leachables was developed using headspace GC, a slightly different technique whereby volatile compounds from the sample are evaporated from the liquid before being injected onto the GC column. This prevents much of the sample matrix from going onto the column and thus produces much cleaner chromatography. This method was then also fully validated in accordance with USP requirements and ICH guidelines.