Objective: To establish and verify the helium mass spectrometry detection method to test the sealing integrity of the container closure system (CCS) of pressurized metered dose aerosols (pMDIs). Methods: Determined the maximum allowable leakage limit (MALL) of pMDIs of CCS in the whole life cycle. The special test chambers and helium filling devices were designed and manufactured, and helium filling devices to test the negative and positive control samples under high pressure (absolute pressure 672 kPa) and normal pressure (absolute pressure 100 kPa) respectively. According to the requirements of methodology validation, the validation of detection limit, system suitability, precision, specificity and detection range indicators were completed.The accelerated sample sealing integrity testing for 3, 6 months and 3, 12, 24 months in the long-term stability inspection period was achieved. Results: Under both helium-filled pressure conditions, the methodological validation indicators were in line with the acceptable standards, and the results of the stability samples were less than the detection limits. This method can detect 100% that the equivalent pore diameter of pMDIs product CCS was 0.095 μm and above. Conclusion: The helium mass spectrometry detection method can quickly and quantitatively investigate the leakage rate of pMDIs products, prove the seal integrity of CCS with high sensitivity, and meet the industry's requirements for pMDIs product quality control.
LEI Xiao-qing, SHAO Qi, CHEN Lan
. Investigation the container closure integrity of the pressurized metered dose inhalers by helium mass spectrometry[J]. Chinese Journal of Pharmaceutical Analysis, 2024
, 44(2)
: 298
-306
.
DOI: 10.16155/j.0254-1793.2024.02.13
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