Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China.
Drug Dev Ind Pharm. 2021 Jun;47(6):1001-1010. doi: 10.1080/03639045.2021.1934859. Epub 2021 Aug 6.
To develop poly(d,l-lactide--glycolide) (PLGA) microspheres to achieve controlled and sustained release of brexpiprazole .
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.
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.
A PLGA microsphere loaded with brexpiprazole was successfully developed and demonstrated potential for extended-release of therapeutics for schizophrenia treatment.
开发聚（丙交酯-乙交酯）（PLGA）微球以实现布瑞哌唑的控制和持续释放。
采用油包水乳液-溶剂挥发法制备布瑞哌唑微球，并对其形态、粒径、包封效率、载药量、药物与聚合物的构象和相容性、释放度和药代动力学进行评价。通过建立与释放度的关系，有助于确定合适的释放条件，以探索布瑞哌唑微球的释放特性。
得到了具有近球形形态的多孔 PLGA 微球，平均粒径为 20.43±0.06μm，载药量为 27.24±0.33%，包封率为 81.87±1.07%。傅里叶变换红外光谱（FTIR）、粉末 X 射线衍射（PXRD）和差示扫描量热法（DSC）分析表明，部分包封在微球中的药物仍处于无定形态，部分药物处于结晶态。不同的释放装置导致不同的释放动力学。透析释放装置在 60 天内累积释放约 65%，而样品分离装置在 35 天内累积释放约 77%。在大鼠的药代动力学研究中，肌肉注射后在最初 2 小时内观察到血浆浓度-时间曲线的突释相，随后是明显的零级释放相。总体而言，布瑞哌唑从 PLGA 微球中实现了长达 40 天的持续释放。
成功开发了载有布瑞哌唑的 PLGA 微球，为治疗精神分裂症的治疗药物的长效释放提供了潜力。
