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

IF 2.7 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmaceutical Innovation Pub Date : 2024-03-01 DOI:10.1007/s12247-024-09815-z

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

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引用次数: 0

Abstract

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.

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洛伐他汀结晶、球形造粒和过滤的一体化连续工艺设计

目的这项工作旨在提高针状洛伐他汀晶体的颗粒加工性能，并开发一种用于生产这种晶体的小尺寸连续式微型工厂。方法开发了洛伐他汀晶体最佳球形聚结和后续产品分离的一般条件，首先是批量工艺，然后转为连续式微型工厂操作。结果甲基异丁基酮是洛伐他汀球形聚结的合适桥接液。包括耦合单元操作和溶剂系统、不匹配的流速和不一致的悬浮固体装载量在内的实际挑战都得到了解决。成功实现了洛伐他汀球形团聚体（D50 = 336 µm）的连续生产。球形团聚增加了洛伐他汀散装粉末的密度，使产品流动性从差变好，同时保持了洛伐他汀片剂的性能。在占地面积为 23 平方米的情况下，每天可生产多达 16,800 剂洛伐他汀（60 毫克）。

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来源期刊

Journal of Pharmaceutical Innovation PHARMACOLOGY & PHARMACY-

CiteScore

3.70

自引率

3.80%

发文量

审稿时长

>12 weeks

期刊介绍： The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories: Materials science, Product design, Process design, optimization, automation and control, Facilities; Information management, Regulatory policy and strategy, Supply chain developments , Education and professional development, Journal of Pharmaceutical Innovation publishes four issues a year.