Andersen Cascade Impaction Test
Common respiratory ailments such as asthma and chronic obstructive pulmonary disease (COPD) are often treated with inhaled medicines. These offer some advantages over conventional oral tablet medicines, such as the fast-acting nature of the delivery system, bypassing the need for the medicine to enter the bloodstream which could be wasted by the digestive system. This allows the delivery of the medicine directly to the target site of action in the lung whilst minimising adverse side-effects due to the typically small amount of active required to ease symptoms. To be effective, the size of the particles once aerosolised is crucial to the therapeutic effect. If the particles are too large they will not reach the targeted area, coming to rest in the mouth throat or thorax. Too small, and they risk bypassing the target area all together. Either way, if the particle size is not optimal the product risks being ineffective.
It is therefore crucial to control the particle size during the development and manufacturing process and to have a robust and accurate method of confirming the aerodynamic particle size as part of QC release testing.
In the pharmaceutical industry, Andersen Cascade Impaction is arguably the most common analytical technique available to assess the aerodynamic particle size of an aerosolised product. The Mark II, 8 stage Cascade impactor operates on the principle of inertial impaction based on the size and velocity of the particles. The impactor itself is constructed of stainless steel or aluminium and comprises of an induction port with cone and eight Stages that are compressed together by three spring clamps and sealed with red silicon O-rings to create an airtight seal. A vacuum pump draws the aerosol through a series of stages at a constant flow rate (28.3 l/min). Each stage contains precision drilled jets. A rubber mouth piece is connected to an induction port which is securely placed on to the top of the impactor stack. Each of the 8 stages has jets (holes) of an increasingly smaller diameter as they go down the stack. An impaction plate, constructed of the same material as the cascade impactor is located directly below the jets. As a pre-determined and constant volume of air travels through the jet the Venturi effect (a reduction in fluid pressure that results when a fluid flows through a constricted section) imparts inertial energy to entrained particles within the airstream. The larger the aerodynamic diameter of the particle, the greater the imparted inertial energy. Larger particles will impact and deposit upon the immediate impaction surface below each stage. Smaller particles with less inertial energy will remain caught in the airflow and proceed through subsequent stages with smaller jets. Eventually, all particles will be impacted (Figure 2).
Figure 2 (https://www.researchgate.net/publication/271732386_Seasonal_behavior_of_radon_decay_products_in_indoor_air_and_resulting_radiation_dose_to_human_respiratory_tract, n.d.)
The stack is then taken apart and each stage is then washed with a solvent to dissolve the deposited active and injected on HPLC to assay each stage.
Source Bioscience’s analytical division is a leading independent, MHRA approved (cGMP) contract research organisation that specialises in the provision of chemistry, manufacturing and control (CMC) laboratory services for all phases of drug development. We support the pharmaceutical research and development process from preclinical enabling studies for investigational medical products (IMPs), through the clinical research phases to batch release testing into the market place.
We have a specialism for inhaler testing with 4 Andersons and 25 HPLCs. Quality comes first and foremost for the high technology delivery system. Whether it is developing and validating methods for novel pharmaceuticals or delivering routine Pharmacopoeia testing on API’s, raw materials, excipients and formulations. With fast on time delivery of projects we work in partnership with our customers to ensure they meet their business objectives.
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