Fatty acid glyceride-based lipid microparticles as a long-acting injectable delivery system for brexpiprazole in...

Schizophrenia is a severe mental disorder with a complex and incompletely understood etiology, typically manifesting as impairments in perception, behavior, and emotional regulation. Although a variety of antipsychotic agents are currently available for clinical management, most require daily administration, which often compromises patient adherence and consequently limits therapeutic efficacy. To address this challenge, we developed a long-acting, microparticle-based injectable formulation of brexpiprazole (BRE) using fatty acid glycerides, specifically glycerol tristearate (GTS), to achieve sustained drug release. The therapeutic potential of this formulation was evaluated in a dizocilpine-induced rat model of schizophrenia. In vitro release studies and in vivo pharmacokinetic analyses confirmed that BRE-loaded lipid microparticles (BRE-GTS) exhibited prolonged and controlled release. A single subcutaneous administration of BRE-GTS maintained therapeutic plasma levels and produced sustained antipsychotic effects for approximately two months, significantly ameliorating schizophrenia-like behaviors and improving cognitive performance. Overall, BRE-GTS represents a promising long-acting therapeutic approach for schizophrenia, combining favorable biosafety with sustained drug release, and holds substantial potential to improve medication adherence and long-term treatment outcomes.