Integrated continuous process design for crystallisation, spherical agglomeration, and filtration of lovastatin

Brown, Cameron J. and McGinty, John and Islam, Muhammad T. and Rajoub, Nazer and Arjmandi-Tash, Omid and Ottoboni, Sara and Shahid, Muhid and Urwin, Stephanie J. and Lee, Ye Seol and Chong, Magdalene W. S. and Papathanasiou, Foteini and Prakash, Aruna S. and Prasad, Elke and Spence, Bronwyn and Sefcik, Jan and Robertson, John and Smith, Rachel and Litster, James D. and Price, Chris J. and Nordon, Alison and Adjiman, Claire S. and Florence, Alastair J. (2024) Integrated continuous process design for crystallisation, spherical agglomeration, and filtration of lovastatin. Journal of Pharmaceutical Innovation, 19 (2). 9. ISSN 1939-8042 (

[thumbnail of Brown-etal-JPI-2024-Integrated-continuous-process-design-for-crystallisation-spherical-agglomeration-and-filtration]
Text. Filename: Brown-etal-JPI-2024-Integrated-continuous-process-design-for-crystallisation-spherical-agglomeration-and-filtration.pdf
Final Published Version
License: Creative Commons Attribution 4.0 logo

Download (4MB)| Preview


Purpose This work seeks to improve the particle processability of needle-like lovastatin crystals and develop a small-footprint continuous MicroFactory for its production. Methods General conditions for optimal spherical agglomeration of lovastatin crystals and subsequent product isolation are developed, first as batch processes, and then transferred to continuous MicroFactory operation. Results Methyl isobutyl ketone is a suitable bridging liquid for the spherical agglomeration of lovastatin. Practical challenges including coupling unit operations and solvent systems; mismatched flow rates and inconsistent suspension solid loading were resolved. The successful continuous production of lovastatin spherical agglomerates (D50 = 336 µm) was achieved. Spherical agglomeration increased the density of the bulk lovastatin powder and improved product flowability from poor to good, whilst maintaining lovastatin tablet performance. Conclusion A continuous, integrated MicroFactory for the crystallisation, spherical agglomeration, and filtration of lovastatin is presented with improved product particle processability. Up to 16,800 doses of lovastatin (60 mg) can be produced per day using a footprint of 23 m2.