Document Detail

Deposition, diffusion and transport mechanism of dry powder micro-particulate salbutamol, at the respiratory epithelia.
MedLine Citation:
PMID:  22574661     Owner:  NLM     Status:  Publisher    
The deposition, dissolution and transport of salbutamol base (SB) and salbutamol sulphate (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 SS (98.57±4.23 μg after 4 hours for SB compared to 98.57±4.01 μg after 15 minutes 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 (92.02±4.47 μg SB compared to 63.76±8.84 μg SS transported over 4 hours); 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 transport rate in the Franz diffusion cell to be limited by wetting of the particle and dissolving into the medium. However, for the cell monolayer the cell membrane property regulates the diffusion and transport rate. Analysis of the drug transport in the presence of triethylamine (TEA), a known inhibitor of OCTs, resulted in a significant decrease in drug transport, suggesting an active transport mechanism. The presence of OCTs in this cell line was further validated via Western blot analysis. Finally, the transport of SS from a commercial product (Ventolin Rotacaps®) was studied and showed good agreement with the model SS system studied here.
Mehra Haghi; Daniela Traini; Mary Bebawy; Paul M Young
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-10
Journal Detail:
Title:  Molecular pharmaceutics     Volume:  -     ISSN:  1543-8392     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101197791     Medline TA:  Mol Pharm     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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