Effects of particle size and adding sequence of fine lactose on the deposition of salbutamol sulphate from a dry powder formulation.

Ternary mixtures composed of coarse lactose (CL) (90.8 microm), salbutamol sulphate (SS) (5.8 microm) and either micronised lactose (ML) (5 microm) or intermediate sized lactose (IML) (15.9 microm) in a ratio of 66.5:1:1 w/w were prepared using different mixing sequences of the various components. In addition, a binary mixture composed of CL and SS (67.5:1 w/w) was also prepared as the control. The in vitro deposition of SS was measured using a twin stage impinger after aerosolisation at 60 and 90 l min-1 via a Rotahaler. The aerodynamic particle size distribution of both the aerosolised SS and lactose was further analysed using an Andersen cascade impactor at 60 l min-1. All ternary mixtures produced a significantly higher (analysis of variance, P<0.01) fine particle fraction (FPF) and fine particle dose (FPD) of SS than the control after aerosolisation at either 60 or 90 l min-1. Formulations containing the ML produced significantly (P<0.05) higher FPF and FPD of SS than those containing the IML at both aerosolisation flow rates. Different mixing sequences were also shown to result in different deposition profiles of both SS and lactose after aerosolisation of the ternary mixtures containing ML at 60 l min-1. The formulation prepared by first blending ML with CL before mixing with SS produced a higher FPF and FPD of SS but a lower FPF of lactose than the same formulation in terms of composition but prepared using different mixing orders of the three components. In contrast, the formulations containing IML produced a similar deposition profile to SS, regardless of the mixing sequences, and so did the formulations containing ML aerosolised at 90 l min-1. These results suggest that the effect of mixing sequences on drug deposition may become more prominent at lower aerosolisation flow rates and by reducing the size of any added fine lactose.