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  • Title: Effect of Self-healing Encapsulation on the Initial Burst Release from PLGA Microspheres Containing a Long-Acting Prostacyclin Agonist, ONO-1301.
    Author: Hazekawa M, Kojima H, Haraguchi T, Yoshida M, Uchida T.
    Journal: Chem Pharm Bull (Tokyo); 2017; 65(7):653-659. PubMed ID: 28674339.
    Abstract:
    The purpose of this study was to perform self-healing encapsulation of ONO-1301, a long-acting prostacyclin agonist, into poly(lactide-co-glycolide) (PLGA) microspheres using the oil-in-water (o/w) emulsion solvent evaporation method in order to try to limit the initial burst release of drug. Adequate self-healing of PLGA seemed to be achieved by stirring during the evaporation of solvent at 40°C close to the glass transition temperature (Tg) of the polymer (40.1°C). The plasticizers dimethylphthalate (DEP) or tributyl O-acetylcitrate (TBAC), at concentrations of 0.1-1.0%, to the internal oleogeneous phase in the o/w emulsion system was effective in restricting the initial burst release of the prepared microspheres. The combination of a self-healing at Tg of the polymer and the addition of 1% of each plasticizer was ultimately found to be the most effective in restricting the initial burst release. It is suggested that this is due to the synergistic effect of smooth surface morphology promoted by self-healing at Tg of the polymer and a decrease of the Tg of PLGA caused by the addition of plasticizers.
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