Kemutec mills for Servier in Ireland

Servier solved a problem with the scale-up of primary production for one of its major products with the help of an additional size reduction mill supplied by Kemutec

Servier has installed a 4H KEK Universal Mill from Kemutec at its plant in Arklow, County Wicklow, Ireland. Servier is part of the French international Groupe de Recherche Servier organisation, the largest independent pharmaceutical group in France. As a part of the company's sympathetic approach to the environment, the design of the Irish factory is more akin to a French country chateau than a pharmaceutical production plant.

Servier manufactures three products in Ireland. Natrilix (indapamide) and Coversyl (perindopril t-butylamine) are both antihypertensives, and Diamicron (gliclazide) is an oral treatment for diabetes.

The size and layout of the chateau-like factory belies its annual output of approximately 40 million boxes of healthcare products. Production space is at a premium, and this was a major consideration for chemical plant manager, Liam Cullen, when he considered how best to boost the production of gliclazide from five to 40 or 50 tonnes p.a.

The solution chosen was an additional size reduction mill that could be dedicated to this product. Noise and space considerations were key requirements in defining the mill's specification because the mill would have to be installed on the first floor of the chemical plant building.

Traditional milling systems have a filtered air intake at the material feed point. Air acts as the carrier for the product through the mill, and it has to be filtered out of the system at the milled product collection point. Given that a standard KEK 4H Mill is capable of generating an air flow of 530m³/hr, the size of the filter unit required to separate milled product from the air is substantial. This can cause significant problems where space is tight.

The explosion risk associated with finely divided powders entrained in an air stream is an additional complication. It is not always acceptable for product resulting from an explosion to be vented to atmosphere, and this would certainly be the case with those manufactured by Servier. Another option would have been to build the milling system to withstand a 10 bar overpressure situation — without any venting to atmosphere. However, this still would have meant a large and costly up-rated filter and the question of where to site it.

Faced with these challenges, Kemutec proposed an 'airless' 10 bar rated mill, based upon a closed loop re-circulation system. Once closed up, and ready to run, no additional air is introduced into the loop and therefore there is no requirement to remove it after milling. The air carrying the product is continually re-circulated back to the mill inlet. Using this approach at Servier made it possible to eliminate the need for air filtration and explosion venting — offering a quiet running mill at the same time.

Cullen was pleased by the way Kemutec tailored its proposal to cope with Servier's requirements. Not only could Kemutec readily demonstrate their ability to meet the process specification through trials in their Technology Centre but, in addition, it had reference sites where the solution being proposed was already in operation. Servier undertook the installation of the mill and its associated hoist themselves, following which, the mill was commissioned by engineers from Kemutec.

Drums of gliclazide cake are hoisted above the mill and then inverted to be gravity fed through a hygienic DMN Westinghouse rotary valve into the fabricated 316 stainless steel model 4H KEK universal grinding mill. The mill is fitted with a turbine and screen grinding medium. Milled product drops straight into a conical collection hopper attached directly to the mill outlet. This hopper is accommodated by way of an aperture in the floor under the mill.

This gives adequate headroom on the ground floor below for the milled gliclazide to be transferred, by way of a second DMN Westinghouse rotary valve, into pharmaceutical quality stainless steel IBCs. From here, the active ingredient is mixed with excipients and then delivered to the tableting area for compression.

The relatively short batch runs at Servier meant it was possible to provide a closed loop system which operates without any temperature rise problems. Where longer runs are required, a chiller can be added to the system to maintain an ambient milling temperature.

In common with other KEK mills, the mill at Servier has been designed for easy cleaning between batches, aided considerably by the mirror polishing to the product contact surfaces.