Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary.
Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary.
Int J Pharm. 2024 Dec 5;666:124729. doi: 10.1016/j.ijpharm.2024.124729. Epub 2024 Sep 19.
In the pharmaceutical industry, filtration is traditionally carried out in batch mode. However, with the spread of continuous technologies, there is an increasing demand for robust continuous filtration strategies suitable for processing suspensions produced in continuous crystallizers. Accordingly, this study aimed to investigate a lab-scale horizontal conveyor belt filtration approach for pharmaceutical separation purposes for the first time. The newly developed continuous horizontal belt filter (CHBF) was tested under different systems (microcrystalline cellulose (MCC)/water, lactose/ethanol and acetylsalicylic acid (ASA)/water) and diverse conditions. Filtration was robust using a well-defined unimodal particle size distribution MCC in water system, where the residual moisture content varied within narrow limits of 45-52% independently from the process conditions. Besides, the residual moisture content highly depended on the applied solvent and particle size. It could be reduced to below 2% by processing the suspensions of either a volatile solvent (lactose in ethanol) or an aqueous slurry of a large particle size ASA. Finally, the CHBF was connected to a mixed suspension mixed product removal (MSMPR) or a plug flow crystallizer (PFC). The residual moisture content of the CHBF-filtered ASA product and operation characteristics (onset of steady-state) were evaluated in both continuous crystallizer-filter systems. The MSMPR-CHBF system operated with a longer startup period. The size of the in situ-produced crystals was of a similar order magnitude in both systems, resulting in a similar residual moisture content (around 20%). Overall, the tested continuous filter was robust, did not modify the crystal morphology in the examined experimental range, and could be effectively integrated with continuous crystallizers.
在制药行业中,过滤传统上是分批进行的。然而,随着连续技术的普及,人们对适合处理连续结晶器中生产的悬浮液的稳健连续过滤策略的需求日益增加。因此,本研究首次旨在探索一种用于制药分离的实验室规模水平传送带过滤方法。新开发的连续水平带式过滤器(CHBF)在不同的系统(微晶纤维素(MCC)/水、乳糖/乙醇和乙酰水杨酸(ASA)/水)和不同的条件下进行了测试。在使用具有明确定义的单峰粒径分布 MCC 的水系统中,过滤是稳健的,其中残余水分含量在 45-52%的狭窄范围内变化,独立于工艺条件。此外,残余水分含量高度依赖于所应用的溶剂和粒径。通过处理易挥发溶剂(乳糖在乙醇中)或大粒径 ASA 的水性浆料的悬浮液,可以将其降低到 2%以下。最后,CHBF 连接到混合悬浮混合产物去除(MSMPR)或推流结晶器(PFC)。在这两个连续结晶器-过滤器系统中,评估了 CHBF 过滤的 ASA 产品的残余水分含量和操作特性(稳态开始)。MSMPR-CHBF 系统的启动期较长。两个系统中原位生成的晶体的尺寸具有相似的数量级,导致残余水分含量相似(约 20%)。总体而言,经过测试的连续过滤器具有稳健性,在考察的实验范围内不会改变晶体形态,并且可以有效地与连续结晶器集成。