Influence of physico-chemical carrier properties on the in vitro aerosol deposition from interactive mixtures.

Interactive mixtures were prepared containing 5% (w/w) salbutamol sulfate using various lactose carrier systems, including sieved fractions and blended mixtures of coarse and fine particles. The solid state and powder properties of the lactose carriers were examined by laser diffraction, differential scanning calorimetry, thermogravimetric analysis, powder X-ray diffraction, vapor sorption gravimetry, rotating drum and atomic force microscopy. The in vitro aerosol deposition was determined using a twin-stage impinger with a Rotahaler at an airflow rate of 60l/min. The fine particle fraction (FPF) of salbutamol sulfate was determined using a validated HPLC assay. All samples were highly crystalline with minimal moisture sorption and the major phase in all samples was alpha-lactose monohydrate. Significant differences in FPF were observed using the various carrier systems. FPF increased with decreasing carrier d(50%) (r(2)=0.919) and increasing proportion of fine carrier particles (below 5 microm) (r(2)=0.841). Carriers consisting of very large proportions of fine particles showed low FPF and did not fit the correlation. The presence of coarse carrier particle fractions was essential to achieve maximum FPF, which occurred when about 10% of fine carrier particles were present in the mixture. Dispersion characteristics may be related to the degree of drug aggregation on the carrier surface.