Surface topography of lactose carrier and its influence on drug delivery of dry powder inhalers

Abstract

For dry powder inhaler formulations consisting of drug-carrier mixtures, the deposition profile of the drug in the lungs is dependent on the surface roughness of the carrier particle. It has been reported that the adhesion forces between drug particles and rougher carrier surfaces are stronger, thereby resulting in poorer detachment of drug from the carrier surfaces and less drug delivered into the target regions of the lungs. There is, however, a lack of quantitative assessment of carrier surface roughness and the use of this property to develop better dry powder formulations for drug delivery to the lungs. Quantification of the surface roughness of four commercial lactose types was carried out using the scanning probe microscope. The scan parameters were comparatively evaluated and it was found that the roughness of the carriers was best represented by Ra (arithmetic mean roughness) values. In vitro tests using the twin impinger showed that when rougher carrier surfaces with crevices were used, the availability of the drug to the lower chamber was reduced. There was an optimum Ra value for greater delivery of drug to the lower chamber of the twin-stage impinger. Surface modification of 38-63 um sieved lactose fraction was carried out by two techniques. Firstly, increasing concentrations of fine lactose were added to the lactose carrier before addition of drug. Fine particle fraction (FPF) of drug increased significantly when fine lactose concentration was increased to 8 %w/w. Adhesion of fine lactose to carrier surface played an important role in affecting the detachment of drug and its deposition in the lower chamber of the twin impinger. Secondly, fine lactose particles were immobilized on the lactose carriers by precision coating. Modified lactose carriers of different roughness values were produced by spraying suspensions that consisted of different proportions of isopropyl alcohol. Different amounts of fine lactose were also sprayed. There was a significant correlation between the FPF of the drug and the Ra values of the modified lactose carriers. Knowledge of this relationship is useful in the process of optimizing the surface roughness of lactose carrier for improved drug delivery for a dry powder inhaler.