Tableting technology focuses on novel coatings and continuous processes

Advances in tableting technology include new formulated film coatings, novel capsule designs, and cost-saving continuous processing. Sean Ottewell reports

While pharmaceutical companies, such as Bayer, focus on developing novel active ingredients , other companies are more concerned with their delivery system into the patient.

One major challenge for tablet products is environmental moisture levels. In order to tackle this, Colorcon has introduced a new, fully-formulated high-performance moisture barrier film coating called Opadry amb II.

Colorcon says that the novel formula used in the barrier film offers best-in-class moisture protection and manufacturing productivity.

Both pigmented and clear options are available, resulting in tablets with glossy finishes and well-defined logos - but which do not impact on dissolution.

The improved moisture shield used helps to guard core active ingredients and support final product stability, two important factors when tablets are packaged in bottles or when pharmacies, patients or care givers remove them from primary packaging.

“For the development of Opadry amb II we identified and used a new technology to measure and substantiate the rate of moisture adsorption. We are pleased to be able to bring this product to market, helping our customers improve manufacturing efficiency with reduced production time, while improving final product quality and in-use shelf life, ” noted Colorcon’s vice-president of global business development Cornelis van den Muyzenberg.

The company has also launched an optimised aqueous acrylic enteric coating system called Acryl-EZE II which uses Evonik’s globally-accepted enteric polymer EUDRAGIT L100-55. This eliminates the need for plasticiser addition and can be applied at lower weight gains compared to existing Acryl-EZE systems. As such, it offers enteric performance over a wide range of pH media for acid-labile drug formulations, as well as helping to prevent drug-induced stomach irritation.

Colorcon says the new system also reduces potential errors of raw material handling and application during manufacturing.

Also making advances in enteric delivery is Capsugel, with its intrinsically enteric capsule technology.

Described by the company as a breakthrough in drug-delivery technology, it integrates industry-approved enteric polymers in the capsule design, enabling Capsugel to offer what it says is the first fully enteric dosage form without the need to apply functional coatings.

“The advantages of this technology include minimal excipients needed for formulation, improvement of upper gastrointestinal safety, and differentiated pharmacokinetic performance. It can also accelerate product development while supporting quality by design through scale-up and commercial manufacturing,” explained Amit Patel, president, dosage form solutions, Capsugel.

As part of the company’s lead-user programme, selected customers are carrying out feasibility studies that target oral vaccine and peptide delivery, as well as early-stage development programmes for small chemical entities that could benefit from an intrinsically enteric dosage form.

The company hopes eventually to offer a range of applications for both large and small molecules as it advances the technology with additional customers to new and existing pharmaceutical compounds.

Ionic liquids

In a separate development, Capsugel has acquired the intellectual property pertaining to proprietary ionic liquids technology developed at the Monash Institute of Pharmaceutical Sciences (MIPS) in Australia. This novel technology uses lipid-like counter-ion salts to improve the solubility of drugs in lipid-based liquid, semi-solid and multi-particulate formulations.

The two have a long history of collaboration in lipid-based drug delivery science, including co-founding the Lipid Formulation Classification System (LFCS) consortium to advance and standardise evaluation protocols for lipid-based drug-delivery systems.

Explaining the benefits of ion liquids technology, Keith Hutchison, Capsugel’s senior vice president of R&D, said, “It will allow us to significantly increase drug solubility, reduce absorption variability, decrease excipient levels and reduce pill burden. This represents a valuable addition to our capabilities in designing and developing innovative immediate and modified-release dosage forms.”

Meanwhile, at its new technology centre in Ennigerloh, Bohle has merged all the steps of continuous tablet production for the first time.

“We have leveraged our acknowledged quality in the areas of granulation and coating and, with Gericke and Korsch, have taken on board another two technology leaders for continuous blending/dosing and tablet press technology," explained project leader Lorenz Bohle.

At the technology centre, customers from the pharmaceutical industry can now experience the benefits of continuous production first hand.

"The unique feature of this plant is that the tablet production can be implemented either without granulation or with dry or wet granulation, in one system,” added Bohle. The modular concept of continuous production offers substantial time savings since it does not require any time-consuming analyses of the product samples between the process steps. Moreover, producers benefit from greater flexibility because the plant can be quickly converted to different products.

“The holistic approach of this new form of production is especially interesting; the objective is to link the individual process steps and to ensure consistency with constant parameters,” noted project partner professor Peter Kleinebudde of the University of Dusseldorf’s Institute of Pharmaceutics and Biopharmaceutics.

So far the company has invested €2 million in the project, with several million more being made available in the coming years to further develop the concept of continuous production.

The importance of punch polishing

 Punch polishing is a critical part of any tool care regime and, if carried out correctly, good polishing can help prolong the life of tablet compression tooling. Recognising the importance of this process, I Holland, a leading manufacturer of tablet tooling for the pharmaceutical and nutraceutical industries, has developed the MF80. The company says the new tool is its most advanced polisher yet.

The company recommends a seven step PharmaCare standard operating procedure (SOP) for punch and die maintenance – and polishing is one of these steps.

PharmaCare equipment manager Andy Dumelow explains: "Automated polishing is becoming recognised as the preferred method of effectively polishing tablet tooling. There are clear advantages in terms of operational performance, as well as economic benefits. Firstly, automated polishing eliminates any potential variation that the manual process can bring, as punches can be polished to a micro fine, consistent finish achieved across a batch of punches within a mere 20-minute cycle, freeing up manpower within the tool room to focus on other tasks. In contrast, the other method of manual polishing is essentially a destructive process where over polishing and the subsequent removal of material is quite commonplace. It is very difficult to achieve a consistent finish across a tool set with a manual polishing process.”

Dumelow also notes that the MF80 has been designed to help increase polishing capacity. With an 80 litre drum and the ability to hold up to 17 B or 12 D punches per holder, it gives a maximum of 85 B or 60 D punches per polishing cycle – which he says is a huge benefit in today’s production environment.

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