Single vs Dual Lactose-Polyethylene Glycol 3000 Microcarrier Systems for Pulmonary Salmeterol and Fluticasone Targeted Delivery.

BACKGROUND

Agglomeration/microparticulation of anti-asthmatic/anti-inflammatory salmeterol (SX) and fluticasone (FP) in a single vehicle rendered inefficient pulmonary drug redispersion and site targeting. This study designed externally drug coated dual-microcarrier against single microcarrier (SX external coat/FP internal coat) systems and examined their pulmonary drug delivery/targeting profiles.

METHODS

Spray-dried lactose-polyethylene glycol 3000 microcarriers were prepared with magnesium stearate lubricant added where applicable. Both single- and dual-microcarrier systems were subjected to cascade impactor analysis against microcarrier particle size and formulation attributes. In vivo pharmacokinetics/pharmacodynamics profiles were assessed.

RESULTS

Small microcarrier (~5 µm) was preferred over larger ones for SX targeting at primary to terminal bronchi. Magnesium stearate promoted drug inhalation via reducing microcarrier aggregation and keeping it small for drug deposition and inhalation. Drug-coated single- and dual-microcarrier systems enabled SX release at upper lung and FP release at lower lung. Drug-coated dual-microcarrier enhanced FP inhaled deposition at lower lung due to the absence of external SX barrier and opportunistic hydrophobic aggregation of SX with magnesium stearate-FP deposited on the same microcarrier. Dual-microcarrier increased pulmonary drug retention with a marginal rise in systemic drug levels and reduced inflammatory lymphocytes/eosinophils/neutrophils infiltration, IL-4/5/9/13 release, mucus production, and bronchoconstriction.

CONCLUSION

Dual-microcarrier is more efficient than single-microcarrier in pulmonary SX/FP delivery.