In vitro evaluation of dry powder inhalers I: drug deposition of commonly used devices

Abstract

Inhalation of aerosolized drugs has become the therapy of choice for the treatment of lung diseases. The most commonly used device, the pressurized metered-dose inhaler (pMDI), however, relied on propellants that were found to deplete the ozone layer. To overcome this drawback dry powder inhalers (DPI) have been developed and MDIs with alternative propellants have been introduced recently. Several products are available by now. This study was carried out to evaluate the accuracy of the dose and the theoretically respirable fraction emitted from commonly used DPIs. In vitro measurements were performed using the Twin Impinger (Appendix A, British Pharmacopoiea, 1993) and a self constructed Four Stage Impinger at the standard flow rate of 60 l min−1. Eleven dry powder formulations that are commercially available on the german market were tested with eight dry powder devices: Pulmicort™ and Aerodur™ Turbuhaler™, Intal™ Spinhaler™, Flui™ SCG and Cromolyn™ Orion Inhaler, Sultanol™ Diskhaler™, Flutide™ Diskus™, Atrovent™ with Inhalator M™, Ventilat™ with Inhalator Ingelheim and Buventol™ and Beclomet™ Easyhaler™. As every dry powder inhaler has a specific air flow resistance that limits flow under in vivo conditions, inhaler devices should be tested at corresponding flow conditions in vitro. Though this is not yet reflected in the pharmacopeias, a general consensus can be seen in the scientific literature. Therefore DPIs having a high resistance were tested at 30 l min−1 and those showing a low resistance at 90 l min−1 with the Twin Impinger additionally. Most products were found to emit a fine particle dose of 20–30% of total emitted dose at 60 l min−1. The results of the Twin Impinger and the Four Stage Impinger were in good agreement. Measurements at increasing flow rates generally resulted in increasing fine particle fractions.