Yasunaga Toshiya, Andoh Tooru, Ogawa Noriko, Yamamoto Hiromitsu, Ichikawa Hideki
Laboratory of Pharmaceutical Technology, Graduate School of Pharmaceutical Sciences, Kobe Gakuin University, Kobe 650-8586, Japan.
Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe 650-8586, Japan.
Eur J Pharm Biopharm. 2022 Jan;170:133-143. doi: 10.1016/j.ejpb.2021.11.008. Epub 2021 Dec 3.
For binder-free dry particulate coating to prepare controlled-release micron-sized particles, we designed nanocomposite coating agents with the intention to form a core-shell structure composed of two types of acrylic polymers with different glass transition temperatures (Tg) and evaluated their coating performance. A series of nanocomposite acrylic latexes synthesized by emulsion polymerization was freeze-dried after salting-out to create the powder form. An ion-exchange resin loaded with diclofenac sodium (DS, a model drug) (IER-DS) with a median diameter of approximately 100 µm was used as the core particle. Dry coating of the IER-DS with nanocomposite coating agents was carried out using a laboratory-made coating apparatus assisted with mild-intensity vibration and zirconia bead impaction. The coated particles were cured by heating at a temperature 20 °C higher than the Tg for 12 h to complete the film-forming process. It was found that the highest coating efficiency (more than 70%) and a remarkably prolonged release period of the drug (the time required for 50% release reached approximately 12 h) could be achieved when nanocomposite coating agents with a soft polymeric core (Tg = 30 °C) and a hard polymeric shell (Tg = 80 °C) were applied. In contrast, nanocomposite coating agents with a combination of a hard polymeric core and a soft polymeric shell resulted in lower coating efficiency. These results demonstrate that nanocomposite polymeric coating agents composed of a soft core and a hard shell are effective for the production of drug-loaded microparticles with a prolonged release function by a binder-free dry-coating process.
为了通过无粘合剂干颗粒包衣制备控释微米级颗粒，我们设计了纳米复合包衣剂，旨在形成由两种具有不同玻璃化转变温度（Tg）的丙烯酸聚合物组成的核壳结构，并评估了它们的包衣性能。通过乳液聚合合成的一系列纳米复合丙烯酸乳胶在盐析后进行冷冻干燥，以制成粉末形式。将负载双氯芬酸钠（DS，一种模型药物）的离子交换树脂（IER-DS），其平均直径约为100 µm，用作核心颗粒。使用实验室自制的包衣设备，在轻度振动和氧化锆珠冲击辅助下，用纳米复合包衣剂对IER-DS进行干包衣。将包衣颗粒在高于Tg 20°C的温度下加热12小时进行固化，以完成成膜过程。结果发现，当使用具有软聚合物核（Tg = 30°C）和硬聚合物壳（Tg = 80°C）的纳米复合包衣剂时，可以实现最高的包衣效率（超过70%）和显著延长的药物释放期（50%释放所需时间达到约12小时）。相比之下，具有硬聚合物核和软聚合物壳组合的纳米复合包衣剂导致较低的包衣效率。这些结果表明，由软核和硬壳组成的纳米复合聚合物包衣剂对于通过无粘合剂干包衣工艺生产具有延长释放功能的载药微粒是有效的。
