Commercial scale transfer of a twin-screw melt granulation process for high drug load fevipiprant tablets.

Autor: Vicente Martin C; Pharmaceutical Development, Technical Research and Development, Novartis AG, Basel, Switzerland., Stocker S; Novartis Technical Operations, Novartis Pharma Produktions GmbH, Wehr, Germany., Bautista M; Pharmaceutical Development, Technical Research and Development, Novartis AG, Basel, Switzerland., Rogue V; Pharmaceutical Development, Technical Research and Development, Novartis AG, Basel, Switzerland., Steib-Lauer C; Analytical Research and Development, Technical Research and Development, Novartis AG, Basel, Switzerland., Häcker HG; Novartis Technical Operations, Novartis Pharma Produktions GmbH, Wehr, Germany., Spickermann D; Regulatory Affairs CMC, Global Drug Development, Novartis AG, Basel, Switzerland., Hirsch S; Technical Research and Development, Novartis AG, Basel, Switzerland., Dhareshwar SS; Global Program Management, Portfolio Strategy and Management, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Jazyk: angličtina
Zdroj: Drug development and industrial pharmacy [Drug Dev Ind Pharm] 2022 May; Vol. 48 (5), pp. 211-225. Date of Electronic Publication: 2022 Aug 05.
DOI: 10.1080/03639045.2022.2104307
Abstrakt: Objective: This work summarizes select methodology of twin-screw melt granulation (TSMG) and process analytical technology that were used in the successful scaling-up and commercial transfer of high drug load (80.5% w/w) immediate release fevipiprant tablets.
Significance: The unique and compelling learnings from this industry work are (1) insights into Novartis AG's commercial scale transfer using TSMG and (2) rapid, nondestructive NIR methodology as a PAT tool for RTR testing. No prior literature combines these two aspects at the level of detail we present/disclose.
Methods: Scaling up of TSMG was guided by specific energy values obtained for the 27 mm (pilot scale) and 50 mm (commercial scale) twin-screw extruders (TSE). Proven acceptable ranges (PARs) were confirmed by varying the critical process parameters (CPPs) for granulation (screw speed) and tableting (dwell time and crushing strength) at three process levels (upper, target, and lower). An at-line NIR method was developed and validated for real-time release testing (RTRT).
Results: The combination of CPPs were selected to have the same effect on critical quality attributes (CQAs), that is, lower (-) and upper (+) process level challenged tablet aspect/appearance and dissolution, respectively. TSMG was performed using a 50 mm extruder at constant feed rate. Compression of the six final blends (∼300 kg) showed no impact of varied granulation and compression process conditions on both CQAs. A near-infrared spectroscopy method was validated to determine content uniformity, assay, identity, and to predict CQAs on uncoated tablets in preparation for a real RTRT of future batches.
Databáze: MEDLINE
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