title: Physicochemical characterization of drug-loaded rigid and elastic vesicles.
abstract: Ketorolac loaded rigid and elastic vesicles were prepared by sonication and the physicochemical properties of the drug loaded-vesicle formulations were examined. Rigid and elastic vesicles were prepared from the double chain surfactant sucrose-ester laurate (L-595) and the single chain surfactant octaoxyethylene-laurate ester (PEG-8-L). Sulfosuccinate (TR-70) was used as a negative charge inducer. Evaluation of the prepared vesicle was performed by dynamic light scattering, extrusion and by (1)H NMR (T(2) relaxation studies). The vesicles mean size varied between 90 and 150 nm. The elasticity of the vesicles was enhanced with increasing PEG-8-L/L-595 ratio, while an increase in loading of ketorolac resulted in a reduction in vesicle elasticity. (1)H NMR measurements showed that the molecular mobility of ketorolac was restricted, which indicates that ketorolac molecules were entrapped within the vesicle bilayers. The T(2) values of the aromatic protons of ketorolac increased gradually at higher PEG-8-L levels, indicating that ketorolac mobility increased in the vesicle bilayer. The chemical stability of ketorolac was dramatically improved in the vesicle formulation compared to a buffer solution. The strong interactions of ketorolac with the bilayers of the vesicles might be the explanation for this increased stability of ketorolac.
authors.affiliation: Department of Pharmacy, Faculty of Medicine, The University of Tokyo Hospital, The University of Tokyo, 7-3-1 Hongo Bunkyoku, Tokyo 113-8655, Japan. uchinot@u-shizuoka-ken.ac.jp
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Uchino
authors.forename: Fons
authors.initials: F
authors.lastname: Lefeber
authors.forename: Gert
authors.initials: G
authors.lastname: Gooris
authors.forename: Joke
authors.initials: J
authors.lastname: Bouwstra
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D055598:Chemical Phenomena; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D004548:Elasticity; D020910:Ketorolac / Q000737:chemistry*; D007848:Laurates / Q000737:chemistry; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D055595:Mechanical Phenomena; D008560:Membrane Fluidity / Q000187:drug effects; D008823:Micelles; D054118:Nanospheres / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D013010:Sonication; D013386:Succinates / Q000737:chemistry; D013395:Sucrose / Q000031:analogs & derivatives / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D007848:Laurates; D008081:Liposomes; D008823:Micelles; D013386:Succinates; D013501:Surface-Active Agents; C561032:octaoxyethylene-laurate ester; C018152:sucrose monolaurate; D011092:Polyethylene Glycols; D013395:Sucrose; C024599:thiosuccinic acid; D020910:Ketorolac