Laboratory Expertise Helps Unlock Potential

Kai Koch
Research & Development
Romaco

Susanne Silva
Market Communications
Romaco

Pharmaceutical manufacturers continuously optimise their processes and develop new formulations. Romaco is supporting its customers in this effort by providing laboratories, where manufacturers can analyse process parameters, carry out scale-up tests and obtain assistance from the company's application specialists. Kilian's KiTech laboratory specialises in tableting, while Innojet's expertise at InnoTech is granulation and coating. The newly opened Romaco China Solids Process Centre in Changsha is Romaco's first laboratory outside Europe and the first one to feature technologies by Kilian as well as Innojet.

Pharmaceutical manufacturers worldwide face a daunting challenge: to reconcile ever higher cost pressure with increased quality requirements. In order to satisfy market demands, they must optimise existing processes and push ahead with the development of high quality, cost-efficient formulations. The Romaco Group invests continuously in the development of new and improved, advanced laboratory technologies and is thus excellently equipped to provide research and development services. Whereas Romaco Kilian develops tableting technologies in Cologne, Romaco Innojet specialises in granulation and coating at its facility in Steinen.

"All-in-one" for Drying, Granulation and Coating
"Two things matter particularly to our customers: they want to generate costefficient processes and at the same time reduce the risk of side-effects for end-users to a minimum. Our laboratory technology offers valuable support here, from process development to scale-up tests", explains Dr Andreas van Kampen, Laboratory Manager at Romaco Innojet. The laboratory scale VENTILUS® V 5 dries, granulates and coats powders, granules, crystals, pellets and microtablets, as well as other similar bulk materials, of any size from 10-ìm to 2.0-mm in batches from 1,500-ml to 5,000-ml. All process steps are possible using a single product container. The homogeneous flow conditions inside this container and the scalable spray rate are just two special features. The uniquely homogeneous coatings open up a whole series of options for API release. Furthermore, the amount of active ingredient can be reduced, depending on the formulation.

Lab Sessions for Pharmacists
Manufacturers from all over the world travel to InnoTech, the Innojet test centre in the small south-west German town of Steinen, with their product ideas and process requirements. "We get together with them to analyse the process parameters, identify specific possibilities and develop exact-fit solutions", says Dr Andreas van Kampen when asked to describe the concept. Laboratory equipment with a filling volume of 2.5 and 5 litres is available for the trial sessions. And since the end of 2018, scale-ups to real production conditions have likewise been feasible on a 100 litre system.

Hot-melt Process Provides Long-term Stability
Romaco has reported a marked increase in trials with hot melt technology. Around 35 percent of all sessions are meanwhile accounted for by melt coatings. The quantity which must be applied in order to obtain a good coating is much smaller with this process than the amount of spray solution or suspension that would be needed to achieve the same effect. In contrast to polymer coatings, no aqueous or organic solvents have to be evaporated. There is a growing interest in hot melt technology: "Natural products are inherently prone to instability and so the degree of reproducibility required by the pharmaceutical industry could not be guaranteed in the past" , Dr Andreas van Kampen comments. However, melt coatings providing long-term stability have only recently appeared on the market. Their lower energy consumption and up to 85 per cent shorter processing times are further points in their favour. Romaco Innojet's IHD Hot Melt Device, which is GMP -compliant, is installed upstream of the VENTILUS® processing machine while manufacturing hot melt coatings for the pharmaceutical industry. Hot melt coatings are used, amongst other things, to mask the taste of APIs which are processed as orodispersible tablets (ODx). Taste masking - whether with hot melt or polymer coatings - is a core competency of Romaco Innojet.


Figure 1: The KiTech laboratory in Cologne with the Romaco Innojet STYL'ONE Evolution single-stroke-press and the VENTILUS® processing machine.

Committed to Tableting

Anyone seeking to optimise their tableting processes will not only find suitable equipment at Romaco Kilian's KiTech test laboratory in Cologne but can also obtain support to match from a pharmaceutical technologist and an application specialist. A fully furnished laboratory, three air-conditioned rooms for tableting trials and five conference areas are available there for compression tests. The test machines include tablet presses in all performance classes for the production of mono-layer, multi-layer or core tablets. Clients in the pharmaceutical, food and chemical industries take advantage of the broad array of KiTech services to carry out feasibility studies and performance tests or to optimise their formulations or their machine settings. Apart from analyses to determine flow properties or the opportunity for scale-up tests, they also have a chance to try out various machine features such as fill shoe systems, sealing segments or agitator wheels. "Integrating innovative machine components can demonstrably improve efficiency", claims Thomas Bröker, Applications Engineer at the Romaco Kilian KiTech lab. "Close collaboration with our Design department is essential here, so that day-to-day production experience can be taken into account and built-on. Our aim is to help our customers get the most out of their machines."


Figure 2: The moisture content of a granulate is determined.

All-rounder for Research and Development

The STYL’ONE Evolution is a versatile, single-stroke press which is used for research and development activities. In combination with ANALIS, the intelligent PAT software, the technology is also ideal for developing and analysing new or existing formulations. The compression force and performance that are necessary to produce tablets with the required wall dimension or breaking strength, for example, can be easily determined in this way. The STYL'ONE additionally simulates the compression force profiles of all standard high-speed presses and carries out fully automatic compression and performance studies. It achieves compression forces of up to 80-kN with a maximum output of 1,750 tablets per hour. This results in realistic powder compression and remarkably precise test batches. Processes can be optimised in this way, scale-up tests conducted and errors diagnosed. "The STYL'ONE is a fundamental part of our lab routine", emphasises Dr Carola Hanl, Laboratory Manager, KiTech. "It's a user-friendly technology that saves us a lot of time and effort for both tableting and data evaluations. In that respect, the innovative R & D tablet press is extremely convenient."


Figure 3: Micro coating trials at InnoTech, the Romaco Innojet test centre in Steinen.

Worthwhile Sessions in the Lab

Thanks to its InnoTech and KiTech laboratories, Romaco is in a position to offer comprehensive services to both prospective clients and long-time users looking to develop new formulations or optimise their processes. The lab sessions on high-tech machines are accompanied and supported by specialists and documented in detail. The laboratories can additionally be used for machine training. The expert seminars organised by Romaco Innojet and Kilian in co-operation with premix and carrier suppliers are regularly fully booked.