The influence of carrier morphology on drug delivery by dry powder inhalers.
Alpha-lactose monohydrate was prepared to have different morphological features but with similar particle size. The crystal shape and surface smoothness of lactose were quantified by a number of shape descriptors and these were 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 salbutamol 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 l min(-1) via the Rotahaler and the Cyclohaler into a twin stage liquid impinger. The formulations prepared using the different batches of lactose produced different deposition profiles of SS. The fine particle (< 6.4 microm) fraction (FPF) of aerosolised SS varied from 12.6 +/- 2.4 to 25.6 +/- 1.5% after aerosolisation from the Cyclohaler whilst it changed from 15.0 +/- 2.2 to 24.4 +/- 0.8% after aerosolisation from the Rotahaler. The fine particle dose (FPD) and dispersibility of SS followed a similar trend to the change in the FPF of the drug. No significant difference (ANOVA P > 0.05) was observed for the deposition profiles of SS after aerosolisation from the Rotahaler and the Cyclohaler. The FPF and dispersibility of SS increased with either the surface 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 in the surface smoothness were similar to those resulting from changes in elongation 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.
Zeng
X M
XM
Department of Pharmacy, King's College London, UK.
Martin
G P
GP
Marriott
C
C
Pritchard
J
J
D000280:Administration, Inhalation; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry; D000465:Algorithms; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D004337:Drug Carriers; D007785:Lactose; D010316:Particle Size; D011208:Powders
D001993:Bronchodilator Agents; D004337:Drug Carriers; D011208:Powders; D007785:Lactose; D000420:Albuterol