Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
Int J Pharm. 2019 Jan 10;554:149-160. doi: 10.1016/j.ijpharm.2018.11.013. Epub 2018 Nov 7.
Prolonged drug release provided by multiple-unit dosage forms is highly beneficial to enhance the compliance and safety of the pharmacotherapy even for patients with swallowing deficiencies. To facilitate the intake for these patients, multiple-unit tablets and capsules have to be crushed or opened. An attempt to overcome these issues has been made by the introduction of orodispersible films (ODFs), which rapidly disintegrate within the oral cavity and facilitate the intake of oral solid dosage forms. The aim of this study was to develop a rapidly disintegrating ODF with prolonged release properties by incorporation of small-sized micropellets (MPs). MPs with a drug load of 70% were produced by wet extrusion and spheronization using Vivapur MCG as pelletizing aid and diclofenac sodium (DS) as model drug. MPs were film-coated with an Eudragit RS/RL coating and incorporated into the ODF-forming hypromellose solution. ODFs were produced by solvent casting technique. Disintegration times were determined using the PharmaTest disintegration tester equipped with sample holders for ODFs. Dissolution studies were performed for MPs and ODFs. X-ray micro-computed tomography was used to visualize internal and external surface structures of MPs before and after release studies. MP-loaded ODFs show fast disintegration within 30 s, whereby film-coated MPs remain intact. Uncoated MPs are disintegrating thus revealing immediate DS release. In comparison, DS release was prolonged for film-coated MPs and corresponding ODFs. Incorporation of different amounts of MPs had no effect on the dissolution, but on mechanical properties of ODFs, which decrease with increasing amounts of MPs. The production of rapidly disintegrating ODFs with prolonged release properties for DS, representing a freely water-soluble drug, was feasible.
多单位剂型提供的延长药物释放对提高药物治疗的依从性和安全性非常有益，即使是吞咽困难的患者也是如此。为了方便这些患者服用，多单位片剂和胶囊必须被压碎或打开。为了克服这些问题，人们尝试引入口腔速溶膜（ODF），它在口腔内迅速崩解，便于口服固体制剂的服用。本研究的目的是通过加入小粒径的微丸（MPs）来开发具有延长释放特性的快速崩解 ODF。使用 Vivapur MCG 作为造粒助剂和双氯芬酸钠（DS）作为模型药物，通过湿挤压和滚圆法制备载药量为 70%的 MPs。将 MPs 用 Eudragit RS/RL 包衣，并将其掺入到形成 ODF 的羟丙甲纤维素溶液中。通过溶剂浇铸技术制备 ODF。使用配备有 ODF 样品架的 PharmaTest 崩解测试仪来测定崩解时间。对 MPs 和 ODF 进行了溶出度研究。X 射线微计算机断层扫描用于可视化释放研究前后 MPs 的内外表面结构。载药 ODF 在 30s 内迅速崩解，包衣 MPs 保持完整。未包衣的 MPs 崩解，从而立即释放 DS。相比之下，DS 的释放对于包衣 MPs 和相应的 ODF 来说是延长的。加入不同量的 MPs 对溶出度没有影响，但对 ODF 的机械性能有影响，随着 MPs 量的增加而降低。对于代表水溶性药物的 DS，生产具有延长释放特性的快速崩解 ODF 是可行的。
