ABSTRACT

Background

Pressurized metered-dose inhalers (pMDIs) include hydrofluoroalkane (HFA) propellant to generate a drug aerosol upon actuation and drugs can be formulated as solution or suspension. Suspended particles can cream or sediment depending on density differences between drug and propellant and shaking the pMDI is an essential step to ensure a uniform drug dose release.

Research design and methods

The effect of the delay (0, 10, 30, 60 seconds) in pMDI actuation after shaking and the effect of no-shaking during the canister life on the emitted dose (ED) for commercial solution and suspension pMDIs was investigated.

Results

The ED for solutions was unaffected by no-shaking or by the progressive increasing delay in actuation after shaking (between 77% and 97%). For all the suspension products, shaking was demonstrated to be critical to assure the close to nominal drug delivery. In detail, the actuation delay after shaking led to an increase up to 380% or a drop to 32% of ED in relation to the label claim with high variability.

Conclusion

The drug delivered can vary widely for no-shaking and over different shake-fire delays with suspension pMDIs while solution formulations appear to remain stable.

中文翻译：

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某些商业溶液和悬浮加压计量吸入器的发射剂量不会产生摇晃和摇晃延迟的后果。

摘要

背景

加压定量吸入器（pMDI）包括氢氟烷烃（HFA）推进剂，可在驱动时产生药物气雾剂，并且可以将药物配制为溶液或悬浮液。根据药物和推进剂之间的密度差异，悬浮的颗粒可能会起霜或沉淀，摇动pMDI是确保均匀释放药物剂量的重要步骤。

研究设计与方法

研究了摇动后pMDI的延迟（0、10、30、60秒）的影响，以及在滤罐寿命中无摇动对商用溶液和悬浮液pMDI的发射剂量（ED）的影响。

结果

溶液的ED不受摇动或摇动后致动的逐渐增加延迟的影响（介于77％和97％之间）。对于所有悬浮液产品，摇动被证明对于确保接近标称药物的输送至关重要。详细地，相对于具有高可变性的标签声明，摇动之后的致动延迟导致ED的增加高达380％或下降到32％。

结论

对于悬浮液pMDI，所提供的药物在不摇动和摇动延迟不同的情况下差异很大，而溶液制剂似乎保持稳定。