title: Prodrug to probe solution HFA pMDI formulation and pulmonary esterase activity.
abstract: A novel salbutamol prodrug was synthesised. Solubility in HFA-134a and susceptibility to rat lung homogenate, blood and plasma esterase enzymes were investigated. Whereas salbutamol had a very low solubility in HFA-134a, the prodrug was found to be miscible in all proportions. In lung homogenate, the prodrug hydrolysed with a half-life of 45 min, re-generating approximately 17% of expected salbutamol after 8 h incubation. The use of a solution pMDI for pulmonary delivery of the salbutamol prodrug is predicted to result in liberation of salbutamol in the lungs following in vivo hydrolysis by lung esterases.
authors.affiliation: The Welsh School of Pharmacy, Cardiff University, Cathays Park, Cardiff, UK.
authors.forename: P C
authors.initials: PC
authors.lastname: Seville
authors.forename: C
authors.initials: C
authors.lastname: Simons
authors.forename: G
authors.initials: G
authors.lastname: Taylor
authors.forename: P A
authors.initials: PA
authors.lastname: Dickinson
mesh_terms: D000335:Aerosol Propellants / Q000737:chemistry; D000420:Albuterol / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001993:Bronchodilator Agents / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004950:Esterases / Q000378:metabolism*; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry; D006868:Hydrolysis; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009330:Nebulizers and Vaporizers; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D005466:Fluorocarbons
chemical_list: D000335:Aerosol Propellants; D000420:Albuterol; D001993:Bronchodilator Agents; D004950:Esterases; D006845:Hydrocarbons, Fluorinated; D011355:Prodrugs; C094049:apaflurane; D005466:Fluorocarbons