Exploring the impact of extrinsic lactose fines, a USP modified sampling device and modified centrifuge tube on the delivered dose uniformity and drug detachment performance of a fluticasone propionate dry powder inhaler

Abstract

The present study aimed to probe influences exerted by extrinsic lactose fines on drug detachment and delivered dose uniformity (DDU) of fluticasone propionate (FP) dry powder inhaler (DPI). Extrinsic lactose fines (0–35%) containing lactose pre-blends were formulated using a low shear 3D shaker mixer and systematically analyzed for various physicochemical properties. Moreover, formulated FP DPIs were assessed for drug detachment by force distribution concept and the DDU using two different sampling devices i.e. the Dosage Unit Sampling Apparatus (DUSA) and USP modified glass sampling device (modified DUSA) coupled with Aerolizer® device at 60 L/min. The physicochemical assessment of control and pre-blend lactose samples displayed significant differences in particle size, surface roughness, degree of surface irregularity and powder flow properties. The formulated FP DPIs displayed monolayer-type FP distribution across the lactose particles in laser Raman spectroscopy with acceptable content uniformity (~100%). Drug detachment study using a modified centrifuge tube showed significant differences in drug detachment profile. The FP DPI formulated using 20% of lactose fines showed the lowest drug detachment force (349.45 gf) as compared to the other lactose samples. Moreover, the FP DPI formulated using 20% of lactose fines demonstrated acceptable mean delivered dose (107.76 and 110.62 μg) with the lowest coefficient of variation using DUSA and modified DUSA, respectively. The present study is the first comprehensive summary of delivered dose uniformity using two different USP sampling devices. Accordingly, these observations may be of high significance for both intuitional and industrial formulators.