Orally Disintegrating Tablet Manufacture via Direct Powder Compression Using Cellulose Nanofiber as a Functional Additive.

ABSTRACT

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.