A novel polymeric microsphere (MS) containing micronized triamcinolone acetonide (TA)\nin a crystalline state was structured to provide extended drug retention in joints after intra-articular\n(IA) injection. Microcrystals with a median diameter of 1.7 microm were prepared by ultra-sonication\nmethod, and incorporated into poly(lactic-co-glycolic acid)/poly(lactic acid) (PLGA/PLA) MSs using\nspray-drying technique. Cross-sectional observation and X-ray diffraction analysis showed that drug\nmicrocrystals were evenly embedded in the MSs, with a distinctive crystalline nature of TA. In vitro\ndrug release from the novel MSs was markedly decelerated compared to those from the marketed\ncrystalline suspension (Triam inj.®), or even 7.2 microm-sized TA crystals-loaded MSs. The novel system\noffered prolonged drug retention in rat joints, providing quantifiable TA remains over 28 days.\nWhereas, over 95% of IA TA was removed from joints within seven days, after injection of the\nmarketed product. Systemic exposure of the steroidal compound was drastically decreased with the\nMSs, with <50% systemic exposure compared to that with the marketed product. The novel MS was\nphysicochemically stable, with no changes in drug crystallinity and release profile over 12 months.\nTherefore, the TA microcrystals-loaded MS is expected to be beneficial in patients especially with\nosteoarthritis, with reduced IA dosing frequency.
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