TY - JOUR
T1 - Single-tablet-scale direct-compression
T2 - An on-demand manufacturing route for personalized tablets
AU - Kottlan, Andreas
AU - Zirkl, Andrea
AU - Geistlinger, Jakob
AU - Machado Charry, Eduardo
AU - Glasser, Benjamin J.
AU - Khinast, Johannes G.
N1 - Publisher Copyright:
© 2023
PY - 2023/8/25
Y1 - 2023/8/25
N2 - Today's pharmaceutical industry is facing various challenges. Two of them are issues with supply chain security and the increasing demand for personalized medicine. Both can be addressed by increasing flexibility and a more decentralized approach to pharmaceutical manufacturing. In this study, we present a setup that provides flexibility in terms of supplied raw materials and the product, i.e., a direct-compression setup for personalized tablets operating at a single-tablet-scale. The performance of the implemented single-tablet-scale technology for dosing and mixing was investigated. In addition, an analysis of the critical quality attributes (CQAs) of immediate release ibuprofen and loratadine tablets was performed. The developed dosing device achieved acceptance rates of > 90 % for doses ≥ 20 mg for various pharmaceutical powders. Regarding the vibratory mixing process, a dependency of the performance on the applied frequencies and acceleration was observed, with 100 Hz and ∼ 90 G performing best, yet still exhibiting varying mixing efficacies depending on the granular system. The tablets produced met U.S. Pharmacopeia requirements regarding mechanical stability and dissolution characteristics. Given these results, we consider the developed setup a proof of concept of a tool to provide personalized tablets to patients while minimizing the dependency on complex supply chains.
AB - Today's pharmaceutical industry is facing various challenges. Two of them are issues with supply chain security and the increasing demand for personalized medicine. Both can be addressed by increasing flexibility and a more decentralized approach to pharmaceutical manufacturing. In this study, we present a setup that provides flexibility in terms of supplied raw materials and the product, i.e., a direct-compression setup for personalized tablets operating at a single-tablet-scale. The performance of the implemented single-tablet-scale technology for dosing and mixing was investigated. In addition, an analysis of the critical quality attributes (CQAs) of immediate release ibuprofen and loratadine tablets was performed. The developed dosing device achieved acceptance rates of > 90 % for doses ≥ 20 mg for various pharmaceutical powders. Regarding the vibratory mixing process, a dependency of the performance on the applied frequencies and acceleration was observed, with 100 Hz and ∼ 90 G performing best, yet still exhibiting varying mixing efficacies depending on the granular system. The tablets produced met U.S. Pharmacopeia requirements regarding mechanical stability and dissolution characteristics. Given these results, we consider the developed setup a proof of concept of a tool to provide personalized tablets to patients while minimizing the dependency on complex supply chains.
KW - Direct compression, Vibratory mixing
KW - On-demand tableting
KW - Personalized medicine
KW - Single-tablet-scale
KW - Supply chain security
UR - http://www.scopus.com/inward/record.url?scp=85166589912&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2023.123274
DO - 10.1016/j.ijpharm.2023.123274
M3 - Article
C2 - 37507098
AN - SCOPUS:85166589912
SN - 0378-5173
VL - 643
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 123274
ER -