Worldwide, pharmaceutical manufacturers face a daunting challenge: that of reconciling ever-higher cost pressures with increased quality requirements
To satisfy market demands, they must optimise existing processes and push ahead with the development of high quality, cost efficient formulations. Dr Kevin Robinson recently caught up with experts from Romaco Group’s Killian and Innojet divisions to discuss advances in laboratory technologies, granulation and coating.
“There are two things that really matter to our customers,” says Dr Andreas van Kampen, Laboratory Manager at Romaco Innojet. “They want to generate cost-efficient processes and, at the same time, reduce the risk of end-user side-effects to a minimum. Our laboratory technology offers valuable support here, from process development to scale-up tests.”
To cite an example, the lab-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 µm to 2.0 mm in batches from 1500–5000 mL.
“All the process steps can be done using a single product container,” says Andreas, adding: “The homogenous flow conditions inside this container and the scalable spray rate are just two special features. In fact, the uniquely homogenous coatings open up a whole raft of options for API release. Furthermore, the amount of active ingredient can be reduced, depending on the formulation.”
Describing the concept in more detail, Dr van Kampen tells me that manufacturers from all over the world travel to InnoTech, the Innojet test centre in the small 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,” he says. Laboratory equipment with filling volumes 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 L system.
A tableting mixture is weighed for small-scale trials in the fully furnished KiTech laboratory
Romaco has reported a marked increase in trials using hot melt technology, with approximately 35% of all sessions now incorporating melt coatings. “There is a growing interest in hot melt technology,” adds Dr van Kampen: “Natural products are inherently unstable and, as a result, it was previously difficult to ensure the degree of reproducibility required by the pharmaceutical industry.”
With this technique, the amount needed to apply a good coating is much smaller than the volumes of spray solution or suspension that would be needed to achieve the same effect using other system. Compared with polymer coatings, no aqueous or organic solvents have to be evaporated.
However, melt coatings providing long-term stability have only recently appeared on the market. “Their lower energy consumption and up to 85% shorter processing times are further points in their favour,” notes Andreas.
“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 used in orodispersible tablets. Taste masking – whether with hot melt or polymer coatings — is a core competency of Romaco Innojet,” he adds.
Anyone seeking to optimise their tableting processes will not only find suitable equipment at Romaco Kilian’s KiTech test laboratory in Cologne, Germany, but can also discuss their specific requirements with 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. Available test machines include a wide range of tablet presses for the production of monolayer, multilayer or core tablets.
What’s more, clients in the pharmaceutical, food and chemical industries have access to the broad array of KiTech services to do feasibility studies, performance tests or optimise their formulations or their machine settings.
“As well as analyses to determine flow properties or the opportunity to conduct scale-up tests, they can also try out various machine features, such as fill shoe systems, sealing segments or agitator wheels,” enthuses Thomas Bröker, Applications Engineer at the Romaco Kilian KiTech lab.
Microcoating trials at InnoTech, the Romaco Innojet test centre in Steinen
“Integrating innovative machine components can demonstrably improve efficiency,” he says, adding: “Close collaboration with our design department is essential here, so that day-to-day production experience can be considered and built on. Our aim is to help our customers get the most out of their machines.”
Dr Carola Hanl, Laboratory Manager, KiTech, introduces me the STYL’ONE. “It’s a fundamental part of our lab routine”, she says. “The STYL’ONE Evolution is a versatile, single-stroke press that’s 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 easily be determined in this way,” she explains.
In addition, the STYL’ONE simulates the compression force profiles of all standard high-speed presses and does fully automatic compression and performance studies. It achieves compression forces of up to 80 kN with a maximum output of 1750 tablets per hour.
This results in realistic powder compression and remarkably precise test batches. Processes can be optimised, scale-up tests conducted and errors diagnosed. Dr Hanl says: “It’s a user-friendly technology that saves us a lot of time and effort during both tableting and data evaluations. In that respect, this innovative R&D tablet press is extremely convenient.”
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.
Furthermore, the labs can also be used for machine training. By continuously investing in the development of new and improved laboratory technologies, the Romaco Group is excellently equipped to provide the research and development services that will enable pharmaceutical manufacturers to produce the medicines needed by patients all over the world.