Design-of-experiment approach to quantify the effect of nano-sized silica on tableting properties of microcrystalline cellulose to facilitate direct compression tableting of binary blend containing a low-dose drug
There are challenges to implementing high-speed direct compression tableting for poor flow, low-density cohesive powder. Thus, excipients with adequate flowability and bulk density are desired to facilitate this process. As a major novelty, the effect of nano-sized silica (Aerosil 200®) on the extent of flow and packing properties enhancement was evaluated. A 32 full-factorial design was applied to investigate the influence of silica load (X1; 0.5–5%) and mixing time (X2; 1–10 min) as independent variables on flow, bulk density and compaction properties of microcrystalline cellulose (MCC).
Optimized MCC-silica blend was subsequently used in tableting of Albuterol Sulphate as a model low-dose drug. Regression analysis demonstrated significant (p ≤ 0.05) effect of X1 and X2 on tableting properties of MCC with pronounced effect of X1. Besides, nano-sized silica exhibited a significant improve in flowability, bulk density and compaction properties of MCC. However, at higher silica loading (over 2.75%) a reduction in flow and compaction was observed. The superior performance of MCC was achieved at silica load of (2.40%) and mixing time of (9.66 min).
Moreover, the optimized blend could be directly compressed into tablets with excellent content uniformity, adequate mechanical strength, fast disintegration (63 ± 0.64 s) and dissolution (>90% after 5 min) that leads to rapid response. Ultimately, dry coating of poor flow-low density powder using nano-sized silica is a promising approach to improve the content uniformity of low-dose tablets prepared by high speed direct compression tableting.
About this article: Mohamed H. Fayed, Mohammed F. Aldawsari, Amer S. AlAli, Ahmed Alsaqr, Bjad K. Almutairy, Alhussain H. Aodah, Hesham M. Tawfeek, El-Sayed Khafagy, Doaa A. Helal, Design-of-experiment approach to quantify the effect of nano-sized silica on tableting properties of microcrystalline cellulose to facilitate direct compression tableting of binary blend containing a low-dose drug, Journal of Drug Delivery Science and Technology,
Volume 68, 2022, 103127, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2022.103127. (https://www.sciencedirect.com/science/article/pii/S1773224722000363)
