Flow Control When Testing Dry-Powder Inhalers.

Abstract

Background: International compendia specify setting the flow for testing dry powder inhalers (DPIs) with the pressure ratio across the flow control valve ≤0.5. This guidance derives from thermodynamic theory, but there is no requirement that the flow control equipment demonstrates adherence to this theory. There is therefore a need to define and test for acceptable flow control valve performance, enabling DPI manufacturers to determine whether their test equipment is achieving the expected flow control. Herein, we present flow control data for two valves common in the inhaler testing community and describe the need for qualification specifications for flow control equipment with such valves.

Methods: We devised a simple laboratory apparatus and method for determining the mass flow rate through two common flow control valves in their commercial configuration. In the test method, the pressure ratio across the valve is lowered from ∼0.7 to 0.3. This range of pressure ratio covers the standard test requirement that the pressure ratio must be 0.5 or less and maps the transition of compressible flow through the valve to the point where the air flow theoretically remains constant.

Results: A common industrial valve, mentioned specifically in Pharm. Eur. 2.9.18 and in earlier editions of United States Pharmacopeia 601, exhibits nearly constant flow when the pressure ratio is <0.5. Another valve in widespread use exhibits a continued slight increase in mass flow rate even as the pressure ratio is decreased below 0.5.

Conclusions: Inhaler testing laboratories should test whether their equipment exhibits the constant flow condition that is often assumed when the pressure ratio across the flow control valve is 0.5 or smaller. Quantitative specifications, yet to be developed, for qualifying commercial flow control equipment must account for both the transient start-up and the steady-state flow in DPI testing.