title: Investigation of solvolysis kinetics of new synthesized fluocinolone acetonide C-21 esters--an in vitro model for prodrug activation.
abstract: In this study the solvolysis of newly synthesized fluocinolone acetonide C-21 esters was analysed in comparison with fluocinonide during a 24-hour period of time. The solvolysis was performed in an ethanol-water (90:10 v/v) mixture using the excess of NaHCO₃. The solvolytic mixtures of each investigated ester have been assayed by a RP-HPLC method using isocratic elution with methanol-water (75:25 v/v); flow rate 1 mL/min; detection at 238 nm; temperature 25 °C. Solvolytic rate constants were calculated from the obtained data. Geometry optimizations and charges calculations were carried out by Gaussian W03 software. A good correlation (R = 0.9924) was obtained between solvolytic rate constants and the polarity of the C-O2 bond of those esters. The established relation between solvolytic rate constant (K) and lipophilicity (cLogP) with experimental anti-inflammatory activity could be indicative for topical corticosteroid prodrug activation.
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia. bojan@pharmacy.bg.ac.rs
authors: Bojan D
authors: BD
authors: Markovic
authors: Vladimir D
authors: VD
authors: Dobricic
authors: Sote M
authors: SM
authors: Vladimirov
authors: Olivera A
authors: OA
authors: Cudina
authors: Vladimir M
authors: VM
authors: Savic
authors: Katarina D
authors: KD
authors: Karljikovic-Rajic
mesh_terms: D004952:Esters; D005446:Fluocinolone Acetonide / Q000737:chemistry*; D007700:Kinetics; D011355:Prodrugs / Q000493:pharmacokinetics*; D012997:Solvents
chemical_list: D004952:Esters; D011355:Prodrugs; D012997:Solvents; D005446:Fluocinolone Acetonide