title: Reduction in burst release of PLGA microparticles by incorporation into cubic phase-forming systems.
abstract: A high initial burst release of an phosphorothioate oligonucleotide drug from poly(lactide-co-glycolide) (PLGA) microparticles prepared by the w/o/w solvent extraction/evaporation was reduced by incorporating the microparticles into the following glycerol monooleate (GMO) formulations: 1) pure molten GMO, 2) preformed cubic phase (GMO+water) or 3) low viscosity in situ cubic phase-forming formulations (GMO+water+cosolvent). The in situ cubic phase-forming formulations had a low viscosity in contrast to the first two formulations resulting in good dispersability of the microparticles and good syringability/injectability. Upon contact with an aqueous phase, a highly viscous cubic phase formed immediately entrapping the microparticles. A low initial burst and a continuous extended release over several weeks was obtained with all investigated formulations. The drug release profile could be well controlled by the cosolvent composition with the in situ systems.
authors.affiliation: College of Pharmacy, Freie Universität Berlin, Berlin, Germany.
authors.forename: Abid Riaz
authors.initials: AR
authors.lastname: Ahmed
authors.forename: Andrei
authors.initials: A
authors.lastname: Dashevsky
authors.forename: Roland
authors.initials: R
authors.lastname: Bodmeier
mesh_terms: D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D000431:Ethanol / Q000737:chemistry; D005989:Glycerides / Q000737:chemistry*; D010316:Particle Size; D054735:Phosphorothioate Oligonucleotides / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013997:Time Factors; D014783:Viscosity; D014867:Water / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005989:Glycerides; D054735:Phosphorothioate Oligonucleotides; D012997:Solvents; D014867:Water; D011098:Polyglactin 910; D000431:Ethanol; C005953:monoolein