title: Effect of beta-sitosterol concentration and high pressure homogenization on the chlorhexidine release from vesicular gels.
abstract: Previous studies have confirmed that the phase transition of vesicular gels of hydrogenated phospholipids to the less ordered fluid vesicular state was induced by the increase of the beta-sitosterol ratio in the whole gel system and consequently in the lipid bilayer. The purpose of the present study was to evaluate the influence of the beta-sitosterol portion in the lipid bilayer and the effect of high pressure homogenization on the structural characteristics of the prepared gel systems. In addition the influence of beta-sitosterol on the consequent chlorhexidine release from the obtained vesicles and liposomes was also examined. Lipid mixtures were prepared from different molar ratios of lecithin:sterol components (90:10-65:35 mol%). The obtained mixtures were hydrated with the aqueous solution of chlorhexidine digluconate in order to achieve a 30% (w/w) final concentration of the lipid mixtures and a 4% (w/w) concentration of the drug. One portion of the resultant multilamellar vesicles was homogenized by using high pressure. To characterize the homogenized and non-homogenized systems, transmission electron microscopy of the freeze-fractured samples and differential scanning calorimetry (DSC) were carried out. A vertical type diffusion cell was applied to determine the amount of released chlorhexidine digluconate. Along with the increase in beta-sitosterol concentration, the fluidity of the membrane as well as its permeability also increased. The increased permeability--caused by the higher beta-sitosterol concentration--and the high pressure homogenization, which increased the dispersity and therefore the surface area, enabled a higher amount of chlorhexidine to be released. The increase of drug release was more pronounced in the case of samples prepared with high pressure homogenization.
authors.affiliation: Pharmaceutical Institute, Semmelweis University, Hogyes E. Street 7, 1092 Budapest, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Farkas
authors.forename: R
authors.initials: R
authors.lastname: Schubert
authors.forename: R
authors.initials: R
authors.lastname: Zelkó
mesh_terms: D000891:Anti-Infective Agents, Local / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002710:Chlorhexidine / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004339:Drug Compounding / Q000379:methods*; D005782:Gels; D000960:Hypolipidemic Agents / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes; D046529:Microscopy, Electron, Transmission; D012855:Sitosterols / Q000737:chemistry*
chemical_list: D000891:Anti-Infective Agents, Local; D003692:Delayed-Action Preparations; D005782:Gels; D000960:Hypolipidemic Agents; D008051:Lipid Bilayers; D008081:Liposomes; D012855:Sitosterols; C025473:gamma-sitosterol; D002710:Chlorhexidine