Faculdade de Farmácia, Universidade de Coimbra, Coimbra, 3000-148, Portugal.
Grupo Tecnimede, Quinta da Cerca, Caixaria, Dois Portos, 2565-187, Portugal.
AAPS PharmSciTech. 2024 Nov 27;25(8):277. doi: 10.1208/s12249-024-02994-5.
Although the development of extended release (ER) matrices has been extensively investigated, understanding the most appropriate mechanism of drug release to achieve the desired release remains a cost- and time-consuming challenge in the early stages of formulation development. This study aimed to investigate the early stage of developing ER hydrophilic matrix tablets containing mirabegron as a model drug, focusing on the effects of polymer type, diluent type, and polymer amount on critical quality attributes (CQAs), namely, tablet swelling and erosion behavior. A full factorial design was employed to explore the interactions of control factors through multivariate regression analysis, emphasizing the application of quality by design (QbD) principles. The swelling and erosion performances of 72 formulations were evaluated. The swelling data were fitted to the Vergnaud model. Finally, in vitro drug release profiles were investigated for four of the formulations studied. The polymer type, diluent type, and polymer amount had distinct effects on the swelling and erosion behavior of the ER matrix tablets. Compared with those with isomalt (G720) or dextrate (DXT), formulations with polyethylene glycol 8000 (P8000) consistently exhibited greater swelling. Additionally, higher molecular weight was correlated with increased swelling within the same polymer type. Hydroxypropylmethylcellulose (HPMC) and polyethylene oxide (PEO)-based formulations showed higher swelling rates, while polyvinyl alcohol (PVA-80) displayed the highest erosion percentage. The findings highlight the significance of incorporating early-stage screening designs to maximize efficiency and optimize time and resource. This approach enables the development of a comprehensive understanding of drug release mechanisms from ER matrix tablets.
尽管已广泛研究了延长释放（ER）基质的开发，但在制剂开发的早期阶段，理解实现所需释放的最适当药物释放机制仍然是一个成本高且耗时的挑战。本研究旨在研究含有米拉贝隆的 ER 亲水基质片剂的早期开发阶段，重点研究聚合物类型、稀释剂类型和聚合物量对关键质量属性（CQAs）的影响，即片剂溶胀和侵蚀行为。采用完全析因设计通过多元回归分析来探索控制因素的相互作用，强调质量源于设计（QbD）原理的应用。评估了 72 种配方的溶胀和侵蚀性能。将溶胀数据拟合到 Vergnaud 模型中。最后，对所研究的四个配方中的四个进行了体外药物释放曲线的研究。聚合物类型、稀释剂类型和聚合物量对 ER 基质片剂的溶胀和侵蚀行为有明显影响。与异麦芽糖醇（G720）或糊精（DXT）相比，含有聚乙二醇 8000（P8000）的配方表现出更大的溶胀。此外，在相同的聚合物类型内，较高的分子量与较高的溶胀相关。羟丙基甲基纤维素（HPMC）和聚氧化乙烯（PEO）基配方表现出较高的溶胀速率，而聚乙烯醇（PVA-80）显示出最高的侵蚀百分比。研究结果强调了在早期阶段纳入筛选设计以最大限度地提高效率并优化时间和资源的重要性。这种方法使我们能够全面了解 ER 基质片剂中药物释放的机制。
