Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University Duesseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany.
Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University Duesseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany.
Eur J Pharm Sci. 2020 Apr 15;146:105266. doi: 10.1016/j.ejps.2020.105266. Epub 2020 Feb 12.
The implementation of tailor-made dosage forms is currently one of the biggest challenges in the health sector. Over the last years, different approaches have been introduced to provide an individual and precise dispensing of the appropriate dose of an active pharmaceutical ingredient (API). A more recent approach, which has been intensively researched in the last years, is 3D-printing of medicines. The aim of this work was to develop printing formulations free of organic solvents for a pressure-assisted microsyringe printing method (PAM), which should also be printable over several days of storage. Furthermore, the printed dosage forms should provide a sustained release of the incorporated API. A mixture of polyvinyl acetate/polyvinylpyrrolidone copolymer (PVAc-PVP), hydroxypropyl methylcellulose (HPMC) and highly dispersed silicon dioxide (SiO) was found to be a feasible polymer matrix to achieve a sustained drug release. Levetiracetam (LEV) was used as model drug. The printed formulations were analyzed regarding mass variation, friability and thickness. Furthermore, the dissolution behavior of freshly printed tablets and tablets printed from stored printing formulations were investigated. The dissolution profiles indicate that the dissolution of LEV could be modified by varying the amount of HPMC and by changing the infill design of tablets. Tablet-like geometries with an infill design of 0.35 mm and 5% HPMC released 50% of the incorporated drug after 4 h, while for tablets with a higher HPMC amount the release was decreased (10% HPMC: 5.5 h; 15% HPMC: 8 h). All printed tablets exhibit a friability < 0.5%, indicating that PAM printing is suitable for the manufacturing of tablets with a high structural integrity. Furthermore, this study demonstrates the ability of producing tablets with a uniform content and mass using PAM printing.
定制剂型的实施是当前卫生领域面临的最大挑战之一。近年来，人们引入了不同的方法来提供活性药物成分（API）的个体化和精准给药。近年来，一种更为新颖的方法——药物 3D 打印技术得到了深入研究。本工作旨在开发无有机溶剂的打印配方，用于压力辅助微量注射器打印方法（PAM），该方法也应在数天的储存后仍可打印。此外，所打印的剂型应提供所包含 API 的持续释放。研究发现，聚醋酸乙烯酯/聚乙烯吡咯烷酮共聚物（PVAc-PVP）、羟丙基甲基纤维素（HPMC）和高分散二氧化硅（SiO）的混合物是实现药物持续释放的可行聚合物基质。左乙拉西坦（LEV）被用作模型药物。对打印配方的质量变化、脆碎度和厚度进行了分析。此外，还研究了新鲜打印片剂和存储后打印制剂的溶出行为。溶解曲线表明，通过改变 HPMC 的用量和改变片剂的填充设计，可以改变 LEV 的溶解行为。填充设计为 0.35mm 且 HPMC 含量为 5%的片剂在 4 小时后释放 50%的包封药物，而 HPMC 含量较高的片剂释放速度降低（10% HPMC：5.5 小时；15% HPMC：8 小时）。所有打印片剂的脆碎度均<0.5%，表明 PAM 打印适合制造具有高结构完整性的片剂。此外，本研究还证明了使用 PAM 打印生产具有均匀含量和质量的片剂的能力。
