Kai Koch, Engineering Manager, Romaco Innojet, in this case study highlights how Romaco Innojet machines, with its air flow bed technology, have enhanced production at Acino Pharma’s Liesberg facility
Acino, the Swiss pharmaceutical producer, has trusted in Romaco Innojet technologies to make its MUPS tablets ever since 2004. Five processing machines in the VENTILUS series are currently used to coat micropellets at Acino’s Liesberg facility. There is a steadily growing demand worldwide for innovative oral release forms.
The backdrop is breathtaking, about 20 miles south of Basel, surrounded by the mountains of the Swiss Jura, is the site of Acino Pharma’s Liesberg production facility. The Acino Group, headquartered in Aesch, is specialised in the development and production of complex galenic formulations. The manufacture of pharmaceutical solids with delayed API release is one of the Liesberg plant’s core competencies. Around 1.5 billion tablets and capsules currently leave the factory every year.
“In spite of this, our capacities here are not yet exhausted and our international target markets are growing at exponential rates. That’s why we’re planning to double our volumes in the medium term,” explains Christophe Dohr, Pharmaceutical Production Head Liesberg, Acino Pharma.
Acino Pharma presently employs some 110 staff in Liesberg, with production in three shifts, five days a week. The majority of the output is destined for licensees both in Switzerland and worldwide. Acino’s portfolio at the Liesberg site comprises oral drugs for treating cardiovascular disorders and Parkinson’s disease as well as various narcotic substances. So-called MUPS tablets form the mainstay of its business.
MUPS and their many advantages
Multiple unit pellet systems, or MUPS for short, are a dosage form consisting of coated API pellets, which are mixed with microcrystalline cellulose and pressed into tablets. Their main characteristic is the controlled release of the active ingredient, which is achieved by applying a functional coating to the pellets. The medication is absorbed in the intestine once the tablets have dissolved in the stomach. Since the tiny pellets pass through the digestive cavity rapidly and unhindered, MUPS tablets do not necessarily have to be taken on an empty stomach. They can also be halved without losing their therapeutic efficacy. Cutting the tablets in two does not damage the sustained-release coating of the micropellets. All of these criteria help improve patient compliance.
The demand for MUPS formulations has risen steadily in the last few years for these diverse reasons. In particular, tablets are a dosage form to which most patients are already accustomed. Acino was among the first to recognise this trend and position itself accordingly. Today, more than 90 per cent of all pellet batches are pressed into MUPS tablets. “Acino specialised in the manufacture of MUPS tablets over a decade ago. The highly complex production process has been continuously improved ever since and we’re now in a comfortable situation where we can deliver premium quality at attractive unit costs,” Dohr emphasises.
Two-stage coating process
Before being pressed into tablets, the pellets undergo a two-stage coating process in which their weight is more than doubled. Neutral pellets made from glucose are used as starter particles. In the first step, the active pharma ingredients are applied one layer at a time, followed by the sustained-release coating. This process takes several days, during which the diameter of the pellets increases from approximately 300 µm to 1000 µm (micrometres). The micro format gives a good idea of the complexity involved.
Since 2004, Acino has trusted in the air flow bed technology originally developed and internationally patented by Dr h.c. Herbert Hüttlin to build up these pellets. Five Romaco Innojet production machines in the VENTILUS series are installed at Acino’s Liesberg facility together with a pilot system of the same type, which is used for research and development. The containers of the production scale machines have a capacity of 800 litres and are designed to handle batches weighing up to about 600 kg. Despite its sheer physical size the technology saves valuable space on the production floor. “The air flow bed unites all the processes which are necessary to build up API pellets and granulates in one system,” confirms Michael Tewelde, Team Expert Granulation, Acino Pharma. “Alternative technologies would need a much bigger footprint, not to mention the additional storage capacity.”
Air flow bed technology