Disagglomeration How to Solve Bottlenecks With Difficult API Products

Author / Editor: Claude Lefebvre* / Dipl.-Ing. (FH) Tobias Hüser

A pharmaceutical company was confronted with a manufacturing problem, which occured with the milling of solids. This being a major obstacle to achieve the production capacity highly needed. To optimize the production flow, Frewitt integrated two process steps into one system.

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In a single step, the Delump Witt mills bulk goods that have hardened and formed lumps as large as 60 cm over time to finenesses of up to 200 µm.
In a single step, the Delump Witt mills bulk goods that have hardened and formed lumps as large as 60 cm over time to finenesses of up to 200 µm.
(Bild: Frewitt)

The Turkish company Sanovel manufactures final OSD forms of anti–diabetic drugs formulated with metformin as one of the active ingredient. The manufacturing site of the company in Istanbul receives metformin packaged in 25 to 80 kg bags which, due to the hygroscopic properties of the product, become hard solid blocks during transport and storage. In order to allow the metformin to be processed, the blocks need to go through a time consuming grinding step which disagglomerates the product into a fine powder of 200 to 300 µm.

Requiring several hours to process a 275 kg batch in the high shear mixer, this time–consuming disagglomeration step was clearly for Sanovel the bottleneck of the whole wet granulation process. A sound technical solution to that issue would shorten the cycle of the high–shear mixer thus allowing a balanced process flow between all components of the whole wet granulation process. Production throughput through the weakest link had to be significantly increased in order to increase overall system performance. The process starts when Metformin blocks are manually charged to a high-shear mixer, initially disagglomerate to 250 micron powder before being processed in a wet granulation suite.

Optimizing the Flow

Back in 2011, the disagglomeration of a 275 kg metformin batch was a time consuming step taking several hours. Sanovel's target was to reduce this to 20 minutes. To find a solution to this challenge, Frewitt was contacted. Since Frewitt had already dealt with the problem with other customers, it didn't have to reinvent the wheel for Sanovel. The solution was readily available: the Delump Witt.

As compared to the conventional approach, which is consisting of a two steps process lump breaker and a mill — the Delump Witt is different by combining in one equipment and one process step breakage of big lumps an fine milling to target particle size. Integration into one system brings a further benefit: Low height, low weight and small footprint. The machine consists of a conical feed funnel for product blocks up to a size of 60 x 30 x 20 cm, a crusher and a conical sieve mill which can be used with different type of sieves or rasps for fine grinding of the product. The rotor and sieve can be easily changed and cleaned.

Disagglomeration in Minutes

Installed at Sanovel in the fourth quarter of 2012, the Delump Witt has since totally achieved the objectives: Metformin blocks are manually charged to the feeding hopper, pre–broken and milled to the final particle size of 250 µm. A batch of 275 kg today is disagglomerated in 10 minutes, crushed and processed to a fine, free–flowing powder easily conveyed by vacuum to a high–shear mixer. From there the product is ready for processing and transfers to downstream operations of the wet granulation suite. Today, the high–shear mixer can deliver its full capacity.

The Delump Witt is fast, easy to clean, and built according the most stringent GMP standards. As currently, cleaning can be a simple manual wash and rinse or cleaning nozzles can be easily added to provide an automated CIP. Since a mobile version of the Delump Witt is in service at Sanovel, it can be easily relocated from one production suite to another — flexibility is guaranteed.

* The author is Director Business Development of Frewitt SA, Granges–Paccot, Switzerland. Contact: Tel. +41-26-460-7400