A study of the relationship between the structure and physicochemical parameters of a homologous series of oxprenolol esters at various pH values and temperatures.
A number of beta-adrenergic blockers, including timolol and propranolol, are administered in eyedrops for the treatment of glaucoma, but their therapeutic value is limited by a relatively high incidence of cardiovascular and respiratory side effects. Because of poor ocular bioavailability, many ocular drugs are applied in high concentrations, which give rise to both ocular and systemic side effects. Methods to increase ocular bioavailability include (a) the development of drug delivery devices designed to release drugs at controlled rates, (b) the use of various vehicles that retard precorneal drug loss, and (c) the conversion of drugs to biologically reversible derivatives (prodrugs) with increased corneal penetration properties, from which the active drugs are released by enzymatic hydrolysis. A homologous series of aliphatic esters of oxprenolol were synthesized and investigated as potential prodrugs for ocular use. The stability of each O-acyl derivative was investigated in aqueous solutions over the pH range 2.2-9.0 at 37 degrees C. The observed rate constants (k[obs]), shelf-lives (t90), lipophilicities, and Arrhenius parameters were determined for each ester. A study of the relationship between the structure and physicochemical parameters of the homologous series of oxprenolol esters at various pH values and temperatures was made.
Jordan
C G
CG
Department of Food Science, Faculty of Agriculture, University College, Belfield, Dublin, Ireland.
D000319:Adrenergic beta-Antagonists / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004355:Drug Stability; D004952:Esters / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008432:Mathematical Computing; D010096:Oxprenolol / Q000031:analogs & derivatives* / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013696:Temperature
D000319:Adrenergic beta-Antagonists; D004952:Esters; D010096:Oxprenolol