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.

中文翻译：

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洛伐他汀结晶、球形团聚和过滤的集成连续工艺设计

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，并为其生产开发一个占地面积小的连续微型工厂。

方法

开发了洛伐他汀晶体最佳球形团聚和后续产品分离的一般条件，首先作为间歇过程，然后转移到连续的 MicroFactory 操作。

结果

甲基异丁基酮是洛伐他汀球形团聚的合适桥联液。实际挑战包括耦合单元操作和溶剂系统；解决了流速不匹配和悬浮固体负载不一致的问题。成功连续生产洛伐他汀球形团块（D ₅₀  = 336 µm）。球形附聚增加了洛伐他汀散装粉末的密度，并将产品流动性从差改善到良好，同时保持洛伐他汀片剂的性能。

结论

用于洛伐他汀结晶、球形团聚和过滤的连续、集成的 MicroFactory 具有改进的产品颗粒加工性能。^{使用 23 m 2}的占地面积每天可生产多达 16,800 剂洛伐他汀（60 mg）。