The role of fine particle lactose on the dispersion and deaggregation of salbutamol sulphate in an air stream in vitro

Sieved (63-90 mu m) lactose (L) particles supported on a 63-mu m sieve was subjected to a compressed airstream with a flow rate of 160 l/min in order to remove existing fine particles. Fractions of the air-treated L were then blended separately with either 1.5%, w/w micronised L (5.0 mu m) or magnes ium stearate (7.6 mu m, MS) and the blends were further sieved gently using a 45-mu m sieve to remove any freely dispersed fine L. Other fractions of the air-treated L were also blended with different quantities of intermedia te sized lactose (15.9 mu m, IML) to obtain final concentrations of IML bet ween 1.5 and 9% w/w. The various batches of L were then mixed separately wi th salbutamol sulphate (SS, 5.8 mu m) in a ratio of 67.5:1 (w/w). The parti cle size and shape of L were characterised by laser diffraction, a time-of- sight technique and scanning electron microscopy. The in vitro deposition o f SS was measured using a twin impinger after aerosolisation at 60 l/min vi a a Rotahaler(R). Air treatment of the coarse L was found to reduce signifi cantly (ANOVA, p < 0.01) the fine particle fraction (FPF) and fine particle dose (FPD) of SS but such an effect was reversible by adding fine L back t o the powder formulations. Gentle sieving of coarse-fine L mixtures on a 45 -mu m sieve removed the majority of freely dispersed fine L thereby reducin g significantly (p < 0.05) the FPF and FPD of the drug. MS exhibited a simi lar effect on the dispersion of SS to that of the fine L. The more IML that was added the higher the FPF or FPD of the drug. However, the greatest ste pped-increase in the drug FPF occurred when 1.5% w/w of IML was added, whic h resulted in > 60% increase in FPF of SS whilst increasing the concentrati on of the added IML from 1.5 to 9% produced an approximate 50% further incr ease in the drug FPF. (C) 1998 Elsevier Science B.V. All rights reserved.