Using salmeterol xinafoate (SX) as an active pharmaceutical ingredient, the effects of carrier lactose particle type, total lactose fines content and device resistance on dry powder inhaler performance were investigated in vitro. To mimic drug levels in commercial preparations, interactive mixtures containing 0.58% w/w SX were prepared by low shear tumble mixing. Three types of milled inhalation grade lactose were used (Lactohale(®) LH 200, Respitose(®) ML006 and ML001) and the concentration of fine lactose (Lactohale(®) 300) added was varied. The in vitro deposition of each mixture was studied using a next generation impactor and inhaler devices exhibiting different resistances, Rotahaler(®)<Aerolizer(®)<Handihaler(®). Aerosol performance was evaluated based on the emitted dose (ED), mass median aerodynamic diameter (MMAD) ± geometric standard deviation (GSD) and fine particle fraction (FPF). Increases of up to eight-fold in FPF were observed with increasing intrinsic fine lactose content. The addition of extra fine lactose increased the FPF further, although the effect diminished as more fines were added. The Aerolizer produced the best aerosol performance with any given powder blend, although suitable formulations were identified for each device as defined by the a priori success criteria: >80% ED and MMAD ± GSD between 1-5 μm. The results confirmed the factors under investigation to be important determinants of product performance, but demonstrated using realistic conditions how individual factor impact may be enhanced or mitigated by inter-dependency.
Keywords: Aerolizer; Dry powder inhaler; Handihaler; Lactose; Orally inhaled product (OIP); Rotahaler; Salmeterol xinafoate (SX).
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