Designing Robust Tablet Formulas Resilient to Raw Material and Equipment Variations with the Aid of Design of Experiment (DOE) Method
International Journal of Nutrition and Food Sciences
Volume 8, Issue 6, November 2019, Pages: 78-85
Received: Dec. 11, 2019;
Published: Dec. 12, 2019
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Tian Hao, Department of Science and Technology, Pharmavite LLC, Valencia, USA
Denise Doerflein Fulk, Department of Science and Technology, Pharmavite LLC, Valencia, USA
In tablet production, the physical properties of tablet products are found to change from batch to batch occasionally, which could be caused by raw material and equipment variations. This article focuses on how to design robust formulas resilient to raw material and equipment variations with the aid of Design of Experiment (DOE) method, how to optimize the concentrations of each individual ingredient, and how to avoid the common production issues related to tablet capping, chipping, and dusting problems. The impacts of particle sizes and equipment on compression behaviors were experimentally evaluated and explained with a theoretical hypothesis. The main goal is to show how tablet product quality is controlled from fundamental scientific principles when many active ingredients are present in a single formula, hard to be engineered and dramatically different from the pharmaceutical products. Our findings may provide insightful clues on tablet formulations and design strategies.
Denise Doerflein Fulk,
Designing Robust Tablet Formulas Resilient to Raw Material and Equipment Variations with the Aid of Design of Experiment (DOE) Method, International Journal of Nutrition and Food Sciences.
Vol. 8, No. 6,
2019, pp. 78-85.
K. Zaheer and P. Langguth, “Designing robust immediate release tablet formulations avoiding food effects for BCS class 3 drugs”, 2019, Eur. J. Pharm. Biopharm., 139, pp 177-185.
K. Ofori-Kwakye, F. Osei-Yeboah, and S. L. Kipo, “Formulation and quality evaluation of two conventional release tablet formulations”, 2010, Intern. J. Pharm. Sci. Rev. Res., 4 (1), pp 94-99.
M. Capece, Zhonghui Huang, and Rajesh Dave, “Insight Into a Novel Strategy for the Design of Tablet Formulations Intended for Direct Compression”, 2017, J. Pharm. Sci, 106 (6), pp 1608-1617.
S. Chattoraj, P. Daugherity, T. McDermott, A. Olsofsky, W. J. Roth, and M. Tobyn, “Sticking and Picking in Pharmaceutical Tablet Compression: An IQ Consortium Review”, 2018, J. Pharm. Sci., 107 (9), pp 2267–2282.
J. Tao, S. Robertson-Lavalle, P. Pandey, and S. Badawy, “Understanding the Delamination Risk of a Trilayer Tablet Using Minipiloting Tools”, 2017, J. Pharm. Sci., 106 (11), pp 3346–3352.
A. Skelbæk-Pedersen, T. Vilhelmsen, V. Wallaert, and J. Rantanen, “Quantification of Fragmentation of Pharmaceutical Materials After Tableting”, 2018, J. Pharm. Sci., 108 (3), pp 1246–1253.
C. K. Tye, C. Sun, G. E. Amidon, “Evaluation of the effects of tableting speed on the relationships between compaction pressure, tablet tensile strength, and tablet solid fraction”, 2005, J. Pharm. Sci., 94 (3), pp 465–472.
H. Goh, P. Wan, S. Heng, C. V. Liew, “The Effects of Feed Frame Parameters and Turret Speed on Mini-Tablet Compression”, 2018, J. Pharm. Sci., 108 (3), pp 1161–1171.
S. Abdel-Hamid, F. Alshihabi, G. Betz, “Investigating the effect of particle size and shape on high speed tableting through radial die-wall pressure monitoring”, 2011, Int. J. Pharm., 413 (1–2), pp 29-35.
D. C. Montgomery, Design and Analysis of Experiments, 8th ed., John Wiley & Sons, Inc, 2013.
Jinjiang Li and Yongmei Wu, “Lubricants in Pharmaceutical Solid Dosage Forms”, Lubricants, 2014, 2 (1), pp 21-43.
The data are from Asahi Kasei website, https://www.ceolus.com/en/ceolus_basic.html
Dennis R. Dinger and James E. Funk, Particle-Packing Phenomena and Their Application in Materials Processing, MRS Bulletin 1997, 22 (12), pp. 19-23.
T. Hao, and R. Riman, “Calculation of interparticle spacing in colloidal systems” Journal of Colloid And Interface Science, 2006, 297 (1), pp 374-377, https://doi.org/10.1016/j.jcis.2004.10.014Y.
C. Calvin Sun, “Microstructure of Tablet—Pharmaceutical Significance, Assessment, and Engineering”, Pharmaceutical Research, 2017, 34 (5), pp 918–928.