Department of Pharmaceutical Technology, School of Clinical Pharmacy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime, 790-8578, Japan.
AAPS PharmSciTech. 2021 Dec 23;23(1):37. doi: 10.1208/s12249-021-02194-5.
In recent years, orally disintegrating (OD) tablets have been continuously improved to increase efficacy. Herein, we focused on the benefits of cellulose nanofiber (CNF), a highly functional material, in OD tablet manufacturing. We studied its effects on the physical properties of tablets during manufacture. The analyzed tablet formulations included different content CNF (0-50%; 6 preparations), lactose hydrate, acetaminophen, and magnesium stearate (Mg-St). We measured the angles of repose and evaluated the flowability of the powder. Tablets were prepared on a tabletop and rotary tableting presses, whereafter their weight, drug content, hardness, friability, and disintegration time were evaluated. Although CNF addition slightly reduced powder flowability, continuous tableting was feasible via direct powder compression. Tablet hardness (40 N) was comparable between CNF-containing (20%) tablets and those prepared with crystalline cellulose under 10 kN compression force. Disintegration time (30 s) was similar between CNF-supplemented tablets and those supplemented with low-substituted hydroxypropyl cellulose, crospovidone, or croscarmellose sodium. At higher CNF fractions, tablet hardness increased, while friability decreased. Adding ≥30% CNF prolonged the tablet disintegration time. To set the optimized manufacturing condition for ensuring the desired tablet physical properties, we created contour plots for evaluating the effects of CNF concentration and compression force on hardness and disintegration time. A CNF concentration of 10-20% and a compression force of 12-13 kN would allow for the preparation of tablets with a hardness ≥30 N and a disintegration time ≤60 s. Altogether, addition of CNF to the OD tablet formulation for direct powder compression enhanced hardness and disintegration.
近年来，口腔崩解（OD）片剂不断改进以提高疗效。本文专注于纤维素纳米纤维（CNF）作为一种高度功能性材料在 OD 片剂制造中的益处。我们研究了 CNF 对片剂制造过程中物理性质的影响。分析的片剂配方包括不同含量的 CNF（0-50%；6 个制剂）、乳糖一水合物、对乙酰氨基酚和硬脂酸镁（Mg-St）。我们测量了休止角并评估了粉末的流动性。在台式和旋转压片机上制备片剂，然后评估其重量、药物含量、硬度、脆碎度和崩解时间。尽管 CNF 的添加略微降低了粉末的流动性，但通过直接粉末压缩仍可连续压片。片剂硬度（40 N）在含 CNF（20%）的片剂和在 10 kN 压缩力下用结晶纤维素制备的片剂之间具有可比性。崩解时间（30 s）在补充 CNF 的片剂和补充低取代羟丙基纤维素、交联聚维酮或交联羧甲基纤维素钠的片剂之间相似。在较高的 CNF 分数下，片剂硬度增加，而脆碎度降低。添加≥30%的 CNF 会延长片剂崩解时间。为了确定确保所需片剂物理性质的优化制造条件，我们创建了评估 CNF 浓度和压缩力对硬度和崩解时间影响的等高线图。CNF 浓度为 10-20%和压缩力为 12-13 kN 可制备硬度≥30 N 和崩解时间≤60 s 的片剂。总之，将 CNF 添加到 OD 片剂配方中进行直接粉末压缩可提高硬度和崩解度。
