Drug Permeation Characterization of Inhaled Dry Powder Formulations in Air-Liquid Interfaced Cell Layer Using an Improved, Simple Apparatus for Dispersion.

Abstract

An improved, simple apparatus was developed to easily and uniformly disperse dry powders onto an air-liquid interfaced cultured cell layer. We investigated drug permeation in cell cultures with access to the air-liquid interface (ALI) following deposition of a dry powder using the apparatus. The improved apparatus for dispersing the powders was assembled. Dry powders containing model drugs were prepared and dispersed onto the cell layer with ALI. After the dispersion, the permeation of each model drug was measured and compared with other samples (solutions with the same compositions). The improved apparatus could with ease uniformly disperse 40% of the loading dose onto the cell layer with ALI. Dry powders showed higher drug permeability compared to the samples. without cytotoxicity or an effect on tight junctions. The high drug permeability of dry powders was independent of the molecular weight of model drugs. The contribution of active transport was small, while an increase in passive drug transport via trans- and paracellular routes was observed. Inhaled dry powder formulations achieved higher drug permeability than their solution formulations in ALI. A high local concentration of drugs on the cell layer, caused by direct attachment of the inhaled dry powder, contributed to increased drug permeability via both trans- and paracellular routes.