The influence of lactose carrier on the content homogeneity and dispersibility of beclomethasone dipropionate from dry powder aerosols

Dry powder formulations for inhalation usually comprise a mixture of coarse lactose (CL), employed as a carrier, and micronized drug. It was the aim o f this study to determine the effects of fine lactose (FL), blended as a te rtiary component on the mixing homogeneity and dispersibility of a model hy drophobic drug, beclomethasone dipropionate (BDP). BDP particles (volume me dian diameter (VMD) 4.6 mu m) existed mainly as agglomerates, the majority of which were not dispersed into primary particles after aerosolization at a high shear force (4.7 psi). The resultant particle size distribution of B DP was multi-modal with VMD varying between 4.7 and 30.2 mu m. Ternary inte ractive mixtures were prepared to consist of CL, FL and BDP with a fixed ra tio of lactose to BDP of 67.5:1 w/w, but two concentrations of FL, i.e. 2.5 and 5%, w/w. The mixing was carried out using different sequences of addin g the three components for two mixing times (15 and 60 min). Binary mixture s composed of CL and BDP were prepared for both mixing times as the control s, and these exhibited a coefficient of variation (COV) in BDP content less than or equal to 5%. Addition of FL to the binary formulations greatly red uced the content uniformity of BDP if the final powder were prepared by fir st mixing CL with FL before mixing with the drug (COV > 20%, after mixing f or 15 min). However, the mixtures, prepared using other mixing sequences, h ad a similar uniformity of BDP content to the binary mixtures. All ternary mixtures containing 2.5% FL consistently produced a significantly higher (A NOVA P < 0.01) fine particle fraction (FPF, 3.1-6.1%) and fine particle dos e (FPD, 13.6-30.1 mu g) of BDP than the binary mixtures (FPF, 0.3-0.4%; FPD , 1.6-2.1 mu g) after aerosolization at 60 l min(-1) via a Rotahaler into a twin stage liquid impinger. The mixing sequences exerted a significant (P < 0.05) effect on the dispersion and deaggregation of BDP from the formulat ions prepared using a mixing time of 15 min but such an effect disappeared when the mixing time was lengthened to 60 min. The dispersibility of BDP wa s always higher from the ternary mixtures than from the binary mixtures. BD P delivery from dry powder inhalers was improved markedly by adding FL to t he formulation, without substantial reduction in the content uniformity of the drug. (C) 2000 Elsevier Science B.V. Ail rights reserved.