Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark; Department of Health Technology, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
Int J Pharm. 2021 May 1;600:120516. doi: 10.1016/j.ijpharm.2021.120516. Epub 2021 Mar 26.
Microcontainers, which are microfabricated cylindrical devices with a reservoir function, have shown promise as an oral drug delivery system for small molecular drug compounds. However, they have never been evaluated against a relevant control formulation. In the current study, we prepared microcrystalline cellulose (MCC) microspheres as a control for in vitro and in vivo testing of SU-8 microcontainers as an oral drug delivery system. Both dosage forms were loaded with paracetamol and coated with chitosan or polyethylene glycol (PEG) (12 kDa). These coatings were followed by an additional enteric coating of Eudragit® S100. In addition, a control dosage form was coated with Eudragit® alone. The dosage forms were evaluated in vitro, in a physiologically relevant two-step model simulating rat gastrointestinal fluids, and in vivo by oral administration to rats. In vitro, the microcontainers coated with PEG/Eudragit® resulted in a prolonged release of paracetamol compared to the respective microspheres, which was consistent with in vivo observations of a later time (T) for maximum plasma concentration (C) for the microcontainers. For microspheres and microcontainers coated with chitosan/Eudragit®, the time for complete in vitro release of paracetamol was very similar, due to an earlier release from the microcontainers. This trend was supported by very similar T values in vivo. The in vitro in vivo relation was confirmed by a linear regression with R = 0.9, when T for each dosage form was plotted as a function of time for 90% paracetamol release in vitro. From the in vivo study, the average plasma concentration of paracetamol 120 min after dosing was significantly higher for microcontainers than for microspheres (0.3 ± 0.1 µg/mL and 0.1 ± <0.1 µg/mL, respectively) - regardless of the coating applied.
微容器是一种具有储液器功能的微加工圆柱器件，已被证明是一种小分子药物化合物的口服药物递送系统。然而，它们从未针对相关对照制剂进行过评估。在当前的研究中，我们制备了微晶纤维素 (MCC) 微球作为 SU-8 微容器作为口服药物递送系统的体外和体内测试的对照。两种剂型均负载对乙酰氨基酚，并涂有壳聚糖或聚乙二醇 (PEG)（12 kDa）。这些涂层后，再用 Eudragit® S100 进行额外的肠溶包衣。此外，对照剂型仅用 Eudragit®包衣。这些剂型在体外、模拟大鼠胃肠道液的生理相关两步模型中以及通过口服给予大鼠进行了体内评估。在体外，与各自的微球相比，涂有 PEG/Eudragit®的微容器导致对乙酰氨基酚的释放时间延长，这与微容器的最大血浆浓度 (C) 的时间 (T) 较晚的体内观察结果一致。对于涂有壳聚糖/Eudragit®的微球和微容器，由于微容器中更早的释放，完全体外释放对乙酰氨基酚的时间非常相似。这种趋势得到了体内非常相似的 T 值的支持。当将每个剂型的 T 作为体外 90%对乙酰氨基酚释放的函数绘制时，通过线性回归得到体外-体内关系得到确认，R=0.9。从体内研究中可以看出，微容器给药 120 分钟后，对乙酰氨基酚的平均血浆浓度明显高于微球（分别为 0.3 ± 0.1 µg/mL 和 0.1 ± <0.1 µg/mL）-无论应用哪种涂层。
