Engineered PLGA microspheres for extended release of brexpiprazole: and studies.

Objective: To develop poly(d,l-lactide--glycolide) (PLGA) microspheres to achieve controlled and sustained release of brexpiprazole .

Methods: Brexpiprazole microspheres were prepared by oil-in-water emulsion-solvent evaporation method and evaluated for morphology, particle size, encapsulation efficiency, drug loading, conformation and compatibility of drug and polymer, release, and pharmacokinetics. By establishing the relationship between and release, it helps identify the appropriate release conditions to explore release profiles of brexpiprazole microspheres.

Results: Porous PLGA microspheres with near spherical morphology were obtained displaying an average diameter of 20.43 ± 0.06 μm, a drug loading capacity of 27.24 ± 0.33% and an encapsulation efficiency of 81.87 ± 1.07%. Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC) analysis showed that some drugs encapsulated in the microspheres remained in the amorphous state and some were in the crystalline state. Different release setups resulted in different release kinetics. The dialysis release setup displayed a cumulative release of about 65% within 60 days, while the sample-and-separate setup showed a cumulative release of about 77% within 35 days. Per pharmacokinetic studies in rats, a burst phase in the plasma concentration-time curve was observed after intramuscular injection in the first 2 h followed by a clear zero-order release phase. Overall, brexpiprazole achieved sustained release from PLGA microspheres for up to 40 days.

Conclusion: A PLGA microsphere loaded with brexpiprazole was successfully developed and demonstrated potential for extended-release of therapeutics for schizophrenia treatment.