Promising advancements to the blue dye ingress test - Quantification of blister integrity by leakage rate

The most common packaging type for solid dosage forms is the blister package. The critical quality attribute of blisters is the integrity, which is required to be tested. Hereby it is crucial to develop methodologies representing an improvement compared to the current standard, the blue dye ingress test, regarding sensitivity limits and quantification. In this study, two analytical methods (optical emission spectroscopy and helium mass spectrometry, which rely on a similar principle), were characterized. For the latter a sample preparation procedure was also developed for filling the blister packages with helium tracer gas. Leaky blister packages were prepared via laser drilling, and the leakage rate was measured. Quantification within the experimental space was found to be feasible using optical emission spectroscopy, and partially feasible using helium mass spectrometry. Furthermore, the repeatability was examined and the measurement results were verified with physical and empirical models describing the molecular flow. In conclusion, the two characterized methods represent promising competition to the established standard test due to quantification. Additionally, the procedures can serve as a sensitive reference method for development as well as production.