Stocker, Stephan, Rogue, Vincent, Steib-Lauer, Caroline, Haecker, Hans-Georg, Spickermann, Dirk, Hirsch, Stefan, Dhareshwar, Sundeep, Claudia, Vicente Martin and Manel, Bautista (2022) Twin-screw melt granulation based high drug load tablet formulation. An industrial perspective on process transfer to a commercial manufacturing site. Drug development and industrial pharmacy, https:. pp. 1-15. ISSN 1520-5762; 0363-9045

Abstract

Our motivation for this paper is to highlight select aspects of pharmaceutical processes (granulation and tablet compression) and process analytical technology (PAT) that were performed as part of the commercial manufacturing site transfer campaign of high drug load (80.5 % w/w) immediate release QAW039/Fevipiprant tablets. Twin-screw melt granulation (TSMG) was the key unit operation to achieve a high drug load granule (91.5 % w/w), resulting in a reduced pill burden for the compositional identical 150 mg and 450 mg doses. A proven acceptable range (PAR) was established during the campaign by varying process parameters for granulation (screw speed), blend lubrication, and tabletting (dwell time and compression force) at three process levels (upper, target, lower). These combinations were selected to have the same effect on critical quality attributes (CQAs) i.e., lower (-) and upper (+) process level challenged tablet aspect and dissolution, respectively. Melt granulation was successfully performed using a 50 mm twin-screw extruder at constant feed rate (50 kg/h) across the PAR. Compression of the six final blends (~300 kg/batch) showed no impact of varied granulation and compression process conditions on both CQAs, thereby establishing the PAR within the parameters investigated for a commercially viable process transfer. This paper shows the use of PAT for process development with the goal of readiness of real time release testing (RTRT) which allowed a cost-effective control of the manufacturing process to meet all quality and product specifications. In this context, a near infrared spectroscopy (NIRS) based PAT to determine uniformity of dosage units by content uniformity, assay and identity was also developed and validated to predict CQAs on core (uncoated) tablets in preparation for RTRT of future commercial batches.

Item Type:	Article
Keywords:	Twin-screw melt granulation (TSMG), commercial technology transfer, high drug load tablet, process-analytical technology (PAT), near-infrared spectroscopy (NIRS)
Date Deposited:	20 Aug 2022 00:46
Last Modified:	20 Aug 2022 00:46
URI:	https://oak.novartis.com/id/eprint/45846