The influence of carrier morphology on drug delivery by dry powder inhalers

alpha-Lactose monohydrate was prepared to have different morphological feat ures but with similar particle size. The crystal shape and surface smoothne ss of laclose were quantified by a number of shape descriptors and these we re supported qualitatively by the visual examination of scanning electron ( SE) micrographs of the crystals. All batches of lactose were subjected to a similar history of processing before blending separately with micronised s albutamol sulphate (SS) in a ratio of 67.5:1, w/w, using similar procedures . In vitro deposition of SS from these formulations was investigated after aerosolisation of the formulations at 60 1 min(-1) via the Rorahaler(R) and the Cyclohaler(R) into a twin stage liquid impinger, The formulations prep ared using the different batches of lactose produced different deposition p rofiles of SS. The fine particle ( < 6.4 mu m) fraction (FPF) of aerosolise d SS varied from 12.6 +/- 2.4 to 25.6 +/- 1.5% after aerosolisation from th e Cyclohaler(R) whilst it changed from 15.0 +/- 2.2 to 24.4 +/- 0.8% after aerosolisation from the Rotahaler(R). The fine particle dose (FPD) and disp ersibility of SS followed a similar trend to the change in the FPF of the d rug. No significant difference (ANOVA P > 0.05) was observed for the deposi tion profiles of SS after aerosolisation from the Rotahaler(R) and the Cycl ohaler(R). The FPF and dispersibility of SS increased with either the surfa ce smoothness (P < 0.01) or elongation ratio (P < 0.01) of lactose crystals . The t-ratio values of FPF and dispersibility of SS generated by changes i n the surface smoothness were similar to those resulting from changes in el ongation ratio, Increasing either the surface smoothness or the elongation ratio of lactose crystals will increase the potentially respirable fraction of SS from dry powder formulations for inhalation. (C) 2000 Elsevier Scien ce B.V. All rights reserved.