Purpose

The research was centered on the optimization of the microsphere formulation through a systematic quality-by-design (QBD) methodology, as well as the assessment of their performance in vitro and in vivo.

Methods

The procedure of fabricating microspheres containing pramlintide acetate involved the utilization of a solvent extraction and evaporation technique. The study utilized a Box-Behnken design to systematically optimize the critical process parameters (CPPs) and critical material attribute (CMA) of the microspheres. The evaluation of the microspheres included the assessment of particle size distribution, encapsulation efficiency, in vitro drug dissolution, and in vivo drug release.

Results

The study found that lowering the in vitro drug release rate was caused by increasing the intrinsic viscosity of the PLGA polymer. Additionally, higher homogenization speeds resulted in smaller particle sizes, leading to improved dissolution rates. An optimized microsphere formulation was created based on the results that were found to be best. This optimized formulation demonstrated controlled in vitro and in vivo drug release, reduced burst release, and efficient entrapment efficiency.

Conclusion

The present study effectively utilized a quality-by-design methodology in order to formulate controlled-release microspheres including pramlintide acetate. Through the methodical optimization of crucial process parameters and material properties, a state of optimal formulation was attained. This optimized formulation exhibited a linear and controlled release of the drug over a duration of 4 weeks, as evidenced by an in vivo pharmacokinetic investigation.

Graphical Abstract

中文翻译：

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用于控制药物释放的普兰林肽微球的设计和表征的 QBD 方法

目的

该研究的重点是通过系统的质量设计（QBD）方法优化微球配方，并评估其体外和体内性能。

方法

制备含有醋酸普兰林肽的微球的过程涉及利用溶剂萃取和蒸发技术。该研究利用 Box-Behnken 设计系统地优化微球的关键工艺参数 (CPP) 和关键材料属性 (CMA)。微球的评价包括粒径分布、包封效率、体外药物溶出和体内药物释放的评估。

结果

研究发现，PLGA聚合物的特性粘度增加导致体外药物释放速率降低。此外，更高的均质速度导致更小的颗粒尺寸，从而提高溶解速率。根据发现的最佳结果创建了优化的微球配方。这种优化的配方表现出受控的体外和体内药物释放、减少的突发释放和高效的包封效率。

结论

本研究有效地利用了质量源于设计的方法来配制包含醋酸普兰林肽的控释微球。通过对关键工艺参数和材料特性的系统优化，达到了最佳配方状态。正如体内药代动力学研究所证明的那样，这种优化的制剂在 4 周的时间内表现出药物的线性和受控释放。

图形概要