Deposition, Diffusion and Transport Mechanism of Dry Powder Microparticulate Salbutamol, at the Respiratory Epithelia

Publisher:
American Chemical Society
Publication Type:
Journal Article
Citation:
Molecular Pharmaceutics, 2012, 9 (6), pp. 1717 - 1726
Issue Date:
2012-01
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The deposition, dissolution and transport of salbutamol base (SB) and salbutamol sulfate (SS) inhalation powders were investigated using the Calu-3 air interface cell culture model and Franz diffusion cell. Drug uptake by cells was studied with respect to deposited dose, drug solubility and hydrophobicity. Furthermore, the role of active transport via organic cationic transporters (OCTs) was studied. SB and SS were processed to have similar diameters (3.09 ± 0.06 µm and 3.07 ± 0.03 µm, respectively) and were crystalline in nature. Analysis of drug wetting, dissolution and diffusion using a conventional in vitro Franz cell (incorporating a cell culture support Transwell polyester membrane) showed diffusion of SB to be slower than that of SS (98.57 ± 4.23 µg after 4 h for SB compared to 98.57 ± 4.01 µg after 15 min for SS). Such observations suggest dissolution to be the rate-limiting step. In comparison, the percentage transfer rate using the air interface Calu-3 cell model suggested SB transport to be significantly faster than SS transport (92.02 ± 4.47 µg of SB compared to 63.76 ± 8.84 µg of SS transported over 4 h), indicating that passive diffusion through the cell plays a role in transport. Furthermore, analysis of SB and SS transport, over a range of deposited doses, suggested the transport rate in the Franz diffusion cell to be limited by wetting of the particle and dissolution into the medium.
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