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 mu m), salbutamol su lphate (SS) (5.8 mu m) and either micronised lactose (ML) (5 mu m) or inter mediate sized lactose (IML) (15.9 mu m) in a ratio of 66.5:1:1 w/w were pre pared using different mixing sequences of the various components. In additi on, a binary mixture composed of CL and SS (67.5:1 w/w) was also prepared a s the control. The in vitro deposition of SS was measured using a twin stag e impinger after aerosolisation at 60 and 90 1 min(-1) via a Rotahaler(R). The aerodynamic particle size distribution of both the aerosolised SS and l actose was further analysed using an Andersen cascade impactor at 60 1 min( -1). All ternary mixtures produced a significantly higher (analysis of vari ance, P < 0.01) fine particle fraction (FPF) and fine particle dose (FPD) o f SS than the control after aerosolisation at either 60 or 90 1 min(-1). Fo rmulations containing the ML produced significantly (P < 0.05) higher FPF a nd FPD of SS than those containing the IML at both aerosolisation flow rate s. Different mixing sequences were also shown to result in different deposi tion profiles of both SS and lactose after aerosolisation of the ternary mi xtures containing ML at 60 I min(-1). The formulation prepared by first ble nding 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 compositio n but prepared using different mixing orders of the three components. In co ntrast, the formulations containing IML produced a similar deposition profi le to SS, regardless of the mixing sequences, and so did the formulations c ontaining ML aerosolised at 901 min(-1). These results suggest that the eff ect of mixing sequences on drug deposition may become more prominent at low er aerosolisation flow rates and by reducing the size of any added fine lac tose. (C) 1999 Elsevier Science B.V. All rights reserved.