Reduction in burst release of PLGA microparticles by incorporation into cubic phase-forming systems.
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.
Ahmed
Abid Riaz
AR
College of Pharmacy, Freie Universität Berlin, Berlin, Germany.
Dashevsky
Andrei
A
Bodmeier
Roland
R
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
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005989:Glycerides; D054735:Phosphorothioate Oligonucleotides; D012997:Solvents; D014867:Water; D011098:Polyglactin 910; D000431:Ethanol; C005953:monoolein