Dry powder inhalers: the influence of device resistance and powder formulation on drug and lactose deposition in vitro.

It is a principal in the formulation of a dry powder aerosol that the device should enable a high fine particle fraction (FPF) of drug to be delivered to the lung whilst any carrier, such as lactose, should remain in the upper airways. Both the device and the dry powder formulation itself contribute to the resultant FPF and few studies have considered the deposition of lactose carrier. It was the purpose of this study to determine the effect of the resistance of the device and the influence of powder formulation on the deposition of drug and carrier. Measurement of the pressure drop across the devices investigated in this study showed that the two types of Inhalator Ingelheim had the highest resistance, whilst lower pressure drops were found across the Diskhaler, Cyclohaler and Accuhaler devices. The lowest pressure drops were measured across the Rotahaler and Spinhaler devices. Employing Rotacaps 400 capsules as the formulated salbutamol product, the FPF of drug was greater from the high resistance devices, being in the order Inhalators Ingelheim>Cyclohaler>Rotahaler=Spinhaler. However, the Diskhaler, employing its own developed formulation, produced the highest FPF, approximately twice that from the Accuhaler. There was no statistical difference between the FPF of salbutamol (approximately 20% nominal dose) from the Rotacaps formulation when aerosolised using high resistance devices (Inhalators Ingelheim) operated at 30 l min-1, a medium resistance device (Cyclohaler) operated at 60 l min-1 and low resistance devices (Spinhaler and Rotahaler) operated at a flow-rate of 90 l min-1. The Ventolin Diskhaler using its own formulation operated at 60 l min-1 gave a FPF of 40.33%, but the FPF obtained was sensitive to flow, being only 25.65% of the nominal dose at 30 l min-1. Whereas no lactose was found in the FPF from the Accuhaler operated at 60 l min-1, 100, 400 and 3500 microg were obtained from the Diskhaler, Rotacaps and micronised lactose formulation, respectively, when operated at the same flow-rate. An in-house formulation comprising salbutamol sulphate blended with micronised lactose in a weight ratio of 1:67.5 and aerosolised from a Cyclohaler produced a similar FPF to the Diskhaler at 60 l min-1. When air flow was reduced to 30 l min-1, the FPF from the in-house formulation was reduced considerably less than that from the Diskhaler formulation.