Thi-Tram Nguyena, Kyu-Mok Hwang a, Sang-Yeop Kim b, Eun-Seok Park a.
a Sungkyunkwan University, Suwon 16419, Republic of Korea
b Boryung Pharmaceutical Co., Ltd., Ansan 15425, Republic of Korea
Purpose. The purpose of this study was to improve the quality of granules prepared by roller compaction in the production of an immediate-release tablet. Due to the small size of API and inherent limitations of dry granulation, a high amount of fines arose, leading to poor flowing of the granules. Therefore, after roller compaction, an additional fines recycling step was conducted to separate and recompact the fine sieve fraction.
Methods. Granules were prepared at various process conditions using a laboratory-scale roller compactor and a compaction simulator. The compaction simulator was also employed to characterize the compaction behaviors of materials as well as resultant granules. A principal component analysis was introduced to holistically interpret the effect of dry granulation parameters on size, flow, compaction, and dissolution.
Results. Fines recycling was found to markedly improve size distribution and flowability of the granules, compared to the effect of only increasing roll pressure. Meanwhile, the reduction in tablet strength caused by recompaction was acceptable. The effectiveness of the fines recycling step was demonstrated at commercial scale by highly reliable dissolution performance and good batch-to-batch consistency in comparison with the original granules, which were further confirmed by bioequivalence to the reference product.
Conclusions. Fines recycling could be a useful solution to the excessive amount of fines in roller compaction, provided that its benefit outweighs the loss in granule tabletability. Understanding how granule properties are influenced is essential to controlling dry granulation process for a better product quality.
Thi-Tram Nguyen, Sungkyunkwan University
Thi-Tram Nguyen is currently a Ph.D. candidate at Physical Pharmacy laboratory, School of Pharmacy, Sungkyunkwan University, South Korea. She received her B.S. in Pharmaceutics from University of Medicine and Pharmacy at Ho Chi Minh city, Vietnam (2014) and her M.S. in Science in Pharmacy from Sungkyunkwan University, South Korea (2017). Her research interests include formulation development (gastro-retentive systems, orodispersible tablets, dry powder inhaler) and pharmaceutical processes (taste masking, spray drying, twin screw granulation, and roller compaction). She is the author or coauthor of 4 research articles. She has recently worked on press coated tablets and compaction simulation.