TY - JOUR
T1 - High-Speed Tableting of High Drug-Loaded Tablets Prepared from Fluid-Bed Granulated Isoniazid
AU - Mohylyuk, Valentyn
AU - Bandere, Dace
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/4/13
Y1 - 2023/4/13
N2 - The aim of this feasibility study was to investigate the possibility of producing industrialscale relevant, robust, high drug-loaded (90.9%, w/w) 100 mg dose immediate-release tablets of isoniazid and simultaneously meet the biowaiver requirements. With an understanding of the reallife constrictions on formulation scientists during product development for the generic industry, this study was done considering a common set of excipients and manufacturing operations, as well as paying special attention to the industrial-scale high-speed tableting process as one of the most critical manufacturing operations. The isoniazid substance was not applicable for the direct compression method. Thus, the selection of granulation method was logically justified, and it was fluid-bed granulated with an aqueous solution of Kollidon® 25, mixed with excipients, and tableted with a rotary tablet press (Korsch XL 100) at 80 rpm (80% of the maximum speed) in the compaction pressure range 170–549 MPa monitoring of ejection/removal forces, tablet weight uniformity, thickness, and hardness. Adjusting the main compression force, the Heckel plot, manufacturability, tabletability, compactability, and compressibility profiles were analysed to choose the main compression force that resulted in the desirable tensile strength, friability, disintegration, and dissolution profile. The study showed that highly robust drug-loaded isoniazid tablets with biowaiver requirements compliance can be prepared with a common set of excipients and manufacturing equipment/operations incl. the industrial-scale high-speed tableting process.
AB - The aim of this feasibility study was to investigate the possibility of producing industrialscale relevant, robust, high drug-loaded (90.9%, w/w) 100 mg dose immediate-release tablets of isoniazid and simultaneously meet the biowaiver requirements. With an understanding of the reallife constrictions on formulation scientists during product development for the generic industry, this study was done considering a common set of excipients and manufacturing operations, as well as paying special attention to the industrial-scale high-speed tableting process as one of the most critical manufacturing operations. The isoniazid substance was not applicable for the direct compression method. Thus, the selection of granulation method was logically justified, and it was fluid-bed granulated with an aqueous solution of Kollidon® 25, mixed with excipients, and tableted with a rotary tablet press (Korsch XL 100) at 80 rpm (80% of the maximum speed) in the compaction pressure range 170–549 MPa monitoring of ejection/removal forces, tablet weight uniformity, thickness, and hardness. Adjusting the main compression force, the Heckel plot, manufacturability, tabletability, compactability, and compressibility profiles were analysed to choose the main compression force that resulted in the desirable tensile strength, friability, disintegration, and dissolution profile. The study showed that highly robust drug-loaded isoniazid tablets with biowaiver requirements compliance can be prepared with a common set of excipients and manufacturing equipment/operations incl. the industrial-scale high-speed tableting process.
KW - isoniazid
KW - tablets
KW - high drug-loaded
KW - granulation
KW - wet granulation
KW - fluid-bed granulation
KW - high-speed tableting
KW - Heckel plot
KW - compressibility
KW - tabletability
KW - compactability
UR - http://www.scopus.com/inward/record.url?scp=85154535894&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics15041236
DO - 10.3390/pharmaceutics15041236
M3 - Article
SN - 1999-4923
VL - 15
JO - Pharmaceutics
JF - Pharmaceutics
IS - 4
M1 - 1236
ER -