Rogers True L, Horton Andrew J, Watson Thomas, Robart Stephanie, DeFrancesco Brooklynn, Bishop Hannah, Tocce Elizabeth
Roquette, Midland, MI 48642, USA.
Pharmaceutics. 2025 Sep 2;17(9):1151. doi: 10.3390/pharmaceutics17091151.
The aim of our research was to understand how excipients, unit operations, and process parameters impact processability and resulting properties, performance, and stability of tablets containing bovine lactoferrin, a cohesive biomacromolecule. Microcrystalline cellulose (MCC), croscarmellose (xCMC), lactose (LAC), hydroxypropyl methylcellulose (HPMC), and sodium stearyl fumarate (SSF) were used to produce various tablet formulations containing lactoferrin across a concentration range of 5 to 45%, targeting immediate- or controlled release performance. Tablets were made either by direct compression or via dry granulation followed by tableting. In addition to release performance, tablet attributes were characterized for tensile strength, friability, weight uniformity, and content uniformity. Acceptable tablet tensile strength, friability, and performance were obtained for lactoferrin concentrations ranging from 15 to 45%, using a variety of excipients and manufacturing approaches. In several cases, dry granulation improved content uniformity. Excipient choice and tablet compression force impacted drug release, particularly when MCC alone was used as dry binder for immediate release. Dry granulation impacted tablet tensile properties, but did not significantly impact release performance. Lactoferrin-excipient compatibility was demonstrated for up to 2 years in ambient laboratory conditions. The study demonstrates that robust tablets can be produced using excipients and processes amenable to scale-up for industrial production. Consistent, stable, and suitably performing tablets were successfully produced using a variety of excipients, processing approaches, and across a broad concentration range with this cohesive biomacromolecule active pharmaceutical ingredient (API). Both immediate- and controlled release performance modes were possible.
我们研究的目的是了解辅料、单元操作和工艺参数如何影响含牛乳铁蛋白（一种具有粘性的生物大分子）片剂的可加工性以及最终的性质、性能和稳定性。微晶纤维素（MCC）、交联羧甲基纤维素（xCMC）、乳糖（LAC）、羟丙基甲基纤维素（HPMC）和硬脂酰富马酸钠（SSF）被用于制备各种含乳铁蛋白的片剂配方，乳铁蛋白浓度范围为5%至45%，目标是实现速释或控释性能。片剂通过直接压片或先干法制粒再压片的方式制备。除了释放性能外，还对片剂的拉伸强度、脆碎度、重量均匀度和含量均匀度等属性进行了表征。使用多种辅料和制造方法，对于浓度范围为15%至45%的乳铁蛋白，获得了可接受的片剂拉伸强度、脆碎度和性能。在几种情况下，干法制粒改善了含量均匀度。辅料的选择和片剂的压片力会影响药物释放，特别是当单独使用MCC作为速释的干粘合剂时。干法制粒影响片剂的拉伸性能，但对释放性能没有显著影响。在实验室环境条件下，乳铁蛋白与辅料的相容性证明可持续长达2年。该研究表明，使用适合扩大规模进行工业生产的辅料和工艺可以生产出坚固的片剂。使用多种辅料、加工方法，并在这种具有粘性的生物大分子活性药物成分（API）的广泛浓度范围内，成功制备出了一致、稳定且性能合适的片剂。速释和控释性能模式均有可能实现。
