Water-in-sorbitan monostearate organogels (water-in-oil gels).
Novel multicomponent organogels containing an aqueous phase are described, and some properties which influence their potential as delivery devices for hydrophilic drugs and vaccines are discussed. The gel is produced by preparing a hot water-in-oil (w/o) emulsion using sorbitan monostearate, a nonionic surfactant which is also the organogelator, as the principal emulsifying agent. On cooling at room temperature, the w/o emulsion sets to an opaque, semisolid, thermoreversible organic gel. Cooling the emulsion results in a reduced solubility of the sorbitan monostearate in the oil, with a corresponding decrease in solvent-surfactant affinities, causing surfactant self-assembly into aggregates. The microstructure of the w/o gel is seen by light microscopy to consist of a network of tubules and fibrils (containing the aqueous phase) dispersed in the organic medium. X-ray diffraction and freeze-fracture studies suggest that the tubular aggregates in the w/o gel are made up of surfactant molecules arranged in inverted bilayers and that the aqueous phase is accommodated within these inverted bilayers, bound by the polar headgroups of the surfactant molecules. The presence of water in the tubular skeleton of the organic gels results in the establishment of percolating electroconductive aqueous channels in the organogel. Increasing the water content of a w/o gel causes the surfactant tubules to swell with a corresponding increase in conductivity until the tubules are saturated. Further increase in the water content results in the excess water accumulating in droplets within the organic medium and a decrease in conductivity as the gel integrity is compromised. The w/o gels (containing a model antigen, radiolabeled bovine serum albumin, in the aqueous phase) have demonstrated depot properties after intramuscular administration to mice, entrapped antigen being released over a period of days.
Murdan
S
S
Centre for Drug Delivery Research, School of Pharmacy, University of London, 29-39 Brunswick Square, London, WC1N 1AX, United Kingdom.
van den Bergh
B
B
Gregoriadis
G
G
Florence
A T
AT
D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000737:chemistry; D002417:Cattle; D016503:Drug Delivery Systems; D004553:Electric Conductivity; D004655:Emulsions; D005614:Freeze Fracturing; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D006601:Hexoses / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D008051:Lipid Bilayers / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013501:Surface-Active Agents / Q000737:chemistry*; D014612:Vaccines / Q000008:administration & dosage; D014867:Water / Q000008:administration & dosage / Q000737:chemistry*; D014961:X-Ray Diffraction
D000941:Antigens; D004655:Emulsions; D005782:Gels; D006601:Hexoses; D008051:Lipid Bilayers; D013501:Surface-Active Agents; D014612:Vaccines; D014867:Water; D012710:Serum Albumin, Bovine; C009298:sorbitan monostearate