Lactose as a carrier in dry powder formulations: The influence of surface characteristics on drug delivery

The aim of the study was to investigate the interdependence of carrier part icle size, surface treatment of the carrier, and inclusion of fines on the drug delivery from dry power inhaler formulations. Two size fractions (< 63 and 63-90 mum) of alpha -lactose monohydrate were subjected to treatment w ith 95% (v/v) ethanol to introduce small asperities or cavities onto the ot herwise smooth surface without substantially changing the particle shape. A fter blending with albuterol sulfate [ALB; volume median diameter (VMD), 1. 9 mum; geometric standard deviation (GSD), 1.5], the solvent-treated lactos e produced a fine particle fraction (FPF; < 6.18 mum) and dispersibility of the drug that was significantly (ANOVA p < 0.01) lower than that which res ulted from formulations containing untreated lactose of a similar size frac tion, after aerosolization at 60 L min(-1) via a Rotahaler. The two size fr actions of the treated lactose resulted in similar deposition profiles of A LB. The effects of such surface asperities or cavities of lactose were offs et by introducing a small amount (5% w/w) of smaller-sized lactose (5-10 mu m) to the powder formulations. The fine lactose increased the FPF and dispe rsibility of ALB to such a level that all lactose batches, regardless of pa rticle size or whether solvent treated, produced a similar fraction of aero solized ALB. The inclusion of recrystallized needle lactose (5-15 mum) was superior to micronized lactose in improving the aerosolization of ALB. The findings of this study indicate that the presence and characteristics of th e finer fraction of lactose carrier particles dominate over the particle si ze and surface smoothness of the carrier particles in determining dispersio n and deaggregation of drugs from dry powder formulations for inhalation. ( C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association.