Issue link: https://www.e-digitaleditions.com/i/1463386
12 April 2022 Inhalation The air flow has started—it has to get through the pre-separator e pre-separator of the NGI is an obvious first place to look into the question, "What is responsible for the start-up times of several hundred milliseconds?" Why? Because it is something the air flow must past through immediately after leaving the inhaler, and its volume is approximately 730 mL (see Table 1 of ref- erence 11). At a typical flow rate of 60 L/min coming out of the inhaler, the average residence time in the pre-separator is on the order of 700 ms. is figure is a factor of approximately two to four larger than the typical flow start-up times observed experimentally (Figure 2). So wait a minute; the flow starts up faster than the residence time in the pre-separator. Hmmm… there must be some way for the air flow to pass through the pre-separator faster than one might first think. Hold onto that thought for a moment. Even without fluid mechanics details, we immediately realize qualitatively that one of the most important aspects of the testing system is simply whether a pre- separator is included. Most testing of DPIs requires the pre-separator, but there are dry powder formula- tions that do not require a pre-separator because the m/s; and given that a basic test station is no longer than about one meter, from the inhaler to the sole- noid valve, air with absolutely no obstructions to flow would begin to move at the inhaler in 3 milli- seconds or less, after the solenoid valve starts to open. However, observed flow rate rise times for testing DPIs with an NGI that includes its pre-separator are on the order of hundreds of milliseconds (Figure 2). erefore, with a first glance at the vacuum pump and natural pressure-wave speed, we can conclude that the vacuum pump is not important in the start-up rate of air flow (provided it is strong enough to enable sonic velocity at the control valve) and that "something" between the sealing orifice inside the solenoid valve and the inhaler is indeed providing significant resistance to the air flow. Why go through this logic? So that the reader can better understand how to think about the system. And at the same time, it helps elucidate the conclusion that it is still possible that solenoid opening rate could be making a difference. Do we know the rate at which the orifice of a solenoid valve comes open, say, for example, the fraction of "openness" versus time? No; we are not aware of any published data on this subject. USP Edition Vacuum Tubing Solenoid Valve Vacuum Pump Vol. 28, 2002 8 ± 0.5 mm ID and 50 ± 10 cm long 2-way solenoid valve; internal diameter orifice of 9.5 mm and a flow coefficeint (Cv) equal to 1.8, minimal resistance to air flow and a response time < 100 ms Pump must be capable of drawing the required flow rate through the assembled apparatus with the dry powder inhaler in the mouthpiece adapter. Connect the pump to the solenoid valve using short and wide (≥ 10 mm ID) vacuum tubing and connectors to minimize pump capacity requirements. Vol. 29, 2005 A length of suitable tubing ≥ 8 mm ID with an internal volume of 25 ± 5 mL 2-way, 2-port, having an ID ≥ 8 mm and an opening response time of ≤ 100 ms Pump must be capable of drawing the required flow rate through the assembled apparatus with the dry powder inhaler in the mouthpiece adapter. Connect the pump to the solenoid valve using short and wide (≥ 10 mm ID) vacuum tubing and connectors to minimize pump capacity requirements. Official as of May 1, 2021* A short length of suitable vacuum tubing, e.g., silicone tubing with an inside diameter of 16 mm. The internal volume of the tubing between the impactor and the flow control valve should be 25 ± 5 mL. 2-way, 2-port, with an opening response time of ≤ 100 ms Pump must be capable of drawing the required flow rate through the assembled apparatus with the test product seated in the mouthpiece/ nosepiece adapter. Connect the pump to the solenoid valve using a short length of suitable vacuum tubing and connectors to minimize pump capacity requirements. *See reference 9 for now-closed public comment invitation before this update to USP <601>. Table 1 Portions of USP descriptions of equipment for testing dry powder inhalers