The production of ‘aerodynamically equivalent’ drug and excipient inhalable powders using a novel fractionation technique

Abstract Inhalation particles can be produced by various techniques such as milling, controlled crystallisation and spray-drying, but current methods cannot, to-date, precisely control the aerodynamic size distribution of produced powders. The aim of this study was to develop and validate a novel preparative technique whereby the efficient and reproducible aerodynamic fractionation of drug and excipient powders could be achieved. Salmeterol xinafoate (SX), fluticasone propionate (FP) and fine α-lactose monohydrate (FL) were chosen as model compounds. Powders were aerosolised using a dry powder feeder into a Next Generation Impactor operated at 60 L min −1 . Powders deposited on NGI stages were then collected and analysed. The fractionation process was successful for all powders producing significant linear correlations between the pre-set aerodynamic cut-off limits and geometric size measurements. For each of SX, FP and FL, sufficient powder quantities were recovered from NGI stages 1–6 producing six fractions with sequential aerodynamic and geometric particle size distributions. The fractionation technique was efficient and reproducible for all powders studied. The method can be equally applied to various drugs and excipients regardless of their previous production/processing history. Therefore, the aerodynamic fractionation technique may be used to compare and contrast samples produced by different processes.