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利用具有挑战性的聚合物组成来控制 3D 打印双药物载药聚丸的药物释放。

Manipulating drug release from 3D printed dual-drug loaded polypills using challenging polymer compositions.

机构信息

School of Pharmacy, University of East Anglia, Norwich, UK.

School of Chemistry, University of East Anglia, Norwich, UK.

出版信息

Int J Pharm. 2023 Apr 25;637:122895. doi: 10.1016/j.ijpharm.2023.122895. Epub 2023 Mar 25.

Abstract

Combining multiple medications in a single dosage form has emerged as an important strategy for treating complex diseases and could help tackle the growing issue of polypharmacy. In this study we investigated the suitability of different dual-drug designs for achieving simultaneous, delayed and pulsatile drug release regimes using two model formulations: an immediate release erodible system of Eudragit E PO loaded with paracetamol; and an erodible swellable system of Soluplus loaded with felodipine. Both binary formulations, despite not fused deposition modelling (FDM) printable, were successfully printed using a thermal droplet-based 3D printing method, Arburg Plastic Freeforming (APF), and exhibited good reproducibility. X-ray powder diffraction (XRPD), Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and Differential Scanning Calorimetry (DSC) were used to assess drug-excipient interaction. The printed tablets were evaluated for drug release using in vitro dissolution testing. We found the simultaneous and delayed release designs were effective at generating the intended drug release profiles, giving insight into the types of dual-drug designs which can be used to create complex release profiles. In contrast the pulsatile tablet release was non-defined, highlighting the design limitations when using erodible materials.

摘要

将多种药物组合在单一剂型中已成为治疗复杂疾病的重要策略,并且有助于解决日益严重的多药治疗问题。在这项研究中,我们使用两种模型制剂研究了不同的双药物设计用于实现药物同时、延迟和脉冲释放的适用性:载有扑热息痛的 Eudragit E PO 可蚀蚀释放系统;以及载有非洛地平的 Soluplus 可溶胀释放系统。尽管这两种二元配方不能进行融合沉积建模(FDM)打印,但它们都可以使用基于热液滴的 3D 打印方法,即 Arburg Plastic Freeforming(APF)成功打印,并且具有良好的可重复性。X 射线粉末衍射(XRPD)、衰减全反射傅里叶变换红外光谱(ATR-FTIR)和差示扫描量热法(DSC)用于评估药物-赋形剂相互作用。使用体外溶解试验对打印片剂的药物释放进行了评估。我们发现,同时和延迟释放设计有效地产生了预期的药物释放曲线,深入了解了可以用于创建复杂释放曲线的双药物设计类型。相比之下,脉冲片剂释放是无定义的,突出了使用可蚀材料时的设计限制。

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