Development of a Long-Acting Brexpiprazole Laurate Microcrystalline Suspension via Progressive Particle size Control for Schizophrenia Therapy

This study aimed to evaluate and develop a novel long-acting injectable microcrystalline suspension of a proprietary prodrug, brexpiprazole laurate (BPZL), to improve the compliance of patients with schizophrenia. The BPZL microcrystalline suspension was prepared through a novel “progressive particle-size control” method, incorporating microfluidics, rapid freezing, and lyophilization. The formula was characterized by scanning electron microscope, X-ray diffraction analysis, differential scanning calorimetry, and dynamic light scattering analysis. Both in vitro and in vivo experiments were conducted to assess the performance of the suspension. The resulting suspensions exhibited consistent particle size distributions (D10: 1.23 ± 0.19 µm, D50: 2.62 ± 0.56 µm, D90: 4.88 ± 1.28 µm) and demonstrated excellent stability over 67 days of storage at 25°C. In vivo pharmacokinetic studies in rats showed that there was no initial burst release after a single intramuscular administration, and the plasma concentration of the active metabolite (brexpiprazole) remained above the therapeutic threshold (the median effective concentration, EC50) for approximately 5 days. These results demonstrated that this technique effectively enhances the microcrystalline formulation's long-term stability and sustained-release performance while preventing sudden release effects. These findings offer theoretical support and practical guidance for the clinical application of BPZL microcrystals and the development of sustained-release formulations for other lipophilic drugs.