High-Speed Tableting of High Drug-Loaded Tablets Prepared from Fluid-Bed Granulated Isoniazid

The aim of this feasibility study was to investigate the possibility of producing industrial-scale 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 real-life 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.

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Materials

Isoniazid (INZ; Vaishaly Pharmaceuticals, Mumbai, India; batch # T2005 195/INH) was used as the active pharmaceutical ingredient, povidone (Kollidon® 25; BASF SE, Ludwigshafen, Germany) was used as binder for wet granulation, modified waxy maize food starch (Resistamyl® 347; Tate & Lyle PLC, Koog aan de Zaan, The Netherlands) was used as diluent-disintegrant, crospovidone (PolyplasdoneTM XL-10; Ashland Specialty Ingredients, Wilmington, DE, USA) was used as superdisintegrant, while magnesium stearate (Sudeep Pharma Pvt. Ltd., Nandesari, Vadodara, India) was used as lubricant. Isozid® 100 mg tablets (Fatol Arzneimittel GmbH, Schiffweiler, Germany) were used as reference. Chemicals used for preparation of dissolution media were of Pharmacopoeia grade and used as received.

Mohylyuk, V.; Bandere, D. High-Speed Tableting of High Drug-Loaded Tablets Prepared from Fluid-Bed Granulated Isoniazid. Pharmaceutics 2023, 15, 1236. https://doi.org/10.3390/pharmaceutics15041236

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