Issue link: https://www.e-digitaleditions.com/i/1056686
General Chapter <1602> SPACERS AND VALVED HOLDING CHAMBERS USED WITH INHALATION AEROSOLS— CHARACTERIZATION TESTS e need for a chapter that covers commonly prescribed spacers and valved holding chambers (VHCs) for use with inhalation aerosols (pressurized metered dose inhalers) was identified in 2011 in a Stimuli article on the subject. 11 Spacers are open-ended tubes that are sometimes incorporated into the inhaler, with the pri- mary purpose of increasing the distance from the actua- tor orifice to the patient, thereby reducing impaction of the high velocity particles that emerge from that location upon actuation of the inhaler. On the other hand, VHCs contain at least one valve that enables the result- ing aerosol cloud to be retained within the chamber until the patient opens the valve by inhalation to receive the medication. 12 Some VHCs with a facemask patient interface also contain a separate valve that opens during exhalation, thereby permitting tidal breathing without requiring patients to remove the facemask from the face. Both types of add-on devices greatly modify the APSD of the inhaled aerosol, primarily by virtually eliminating the coarse particle mass fraction greater than about 5 mm aerodynamic diameter that would otherwise impact on surfaces of the oropharyngeal region. 12 e content of chapter <1602> is structured so that the user is first asked to identify if the add-on device is e droplet APSD is measured using the Next Genera- tion Impactor (NGI) operated at a constant flow rate of 15 L/min (Figure 3), in conformity with the original European Standard. 6 e NGI has an archival calibra- tion at this flow rate. 8 Controlling evaporation of droplets produced by nebu- lizers may be critical to avoid bias in the droplet size assessment process. 9 Evaporation caused by heat trans- fer from the impactor metalwork to the droplet stream 10 can be prevented by pre-cooling the impactor to a tem- perature of about 5°C using a refrigerator or by operat- ing the impactor in a climate-controlled chamber. Figure 3 Arrangement for sampling nebulizer-generated aqueous droplets containing drug substance for the purpose of determining the APSD of the drug product. Nebulizer 15 L/min USP/PhEur Induction Port On/Off Valve Vacuum Source Next Generation Impactor Needle Flow Control Valve Figure 4 Decision tree to select type of performance testing for the four combinations of inhalation aerosol add-on device and patient interface. APSD = aerodynamic particle size distribution; EM = emitted mass; VHC = valved holding chamber. Configuration A Spacer with mouthpiece Part 1A: APSD Measurement with NO delay Part 1B: APSD Measurement with delay Configuration C VHC with mouthpiece Part 2A: EM with mouthpiece by Tidal Breathing Simulation —Fully Coordinated Part 2B: EM with mouthpiece by Tidal Breathing Simulation—Fully Uncoordinated Configuration B Spacer with facemask Part 3A: EM with facemask by Tidal Breathing Simulation—Fully Coordinated Part 3B: EM with facemask by Tidal Breathing Simulation—Fully Uncoordinated Configuration D VHC with facemask 14 December 2018 Inhalation