Integrated Continuous Process Design for Crystallisation, Spherical Agglomeration, and Filtration of Lovastatin

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2024年3月1日

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Cameron J. Brown,
John McGinty,
Muhammad T. Islam,
Nazer Rajoub,
Omid Arjmandi-Tash,
Sara Ottoboni,
Muhid Shahid,
Stephanie J. Urwin,
Ye Seol Lee,
Magdalene W. S. Chong,
Foteini Papathanasiou,
Aruna S. Prakash,
Elke Prasad,
Bronwyn Spence,
Jan Sefcik,
John Robertson,
Rachel Smith,
James D. Litster,
Chris J. Price,
Alison Nordon,
Claire S. Adjiman,
Alastair J. Florence

摘要

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.