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Cynthia A. Challener is a contributing editor to Pharmaceutical Technology.
Greater automation and the adoption of solid versus perforated pans are some recent advances.
Tablet coatings in the pharmaceutical industry can serve many purposes. Although originally largely used to help maintain the integrity of the tablet, today, coatings often impart other functionality, such as sustained-release capability, and may even contain an API. Tablet-coating equipment manufacturers are thus being challenged to develop systems that can operate at desired speeds while still providing the necessary level of accuracy and uniformity that is required for each tablet. They are responding with the development and implementation of both new coating technologies and new methods for evaluating coating performance.
Efficient mixing, spray distribution, heating, and air flow
A good coating process first requires efficient mixing without stressing the tablet core, good distribution of the spray solution over the tablet bed, and controlled air flow for effective drying without excessive spray drying, according to Martin Hack, vice-president and general manager for LB Bohle. “Heat exchange during the drying process is critical for good mixing and dictates the consistency of the tablet load,” adds Francesco Nigris, president of Nicos Group, the US Branch of Nicomac. He also notes that cleanability of a pharmaceutical tablet-coating system is also very important.
Changes in the formulation of tableted therapies are also affecting the coating process. “The use by drug manufacturers of active coatings for either dual ethical formulations, which have one active in the core and one active in the coat, or for the application of an active that is more easily dispersed in solution then mixed as a solid and compressed is increasing. The use of functional coats for time-release and other applications is also becoming more prevalent. These types of applications require very high performance coaters that can deliver a very uniform coat to the tablets,” explains Hack, He also notes that a very uniform coat has a relative standard deviation (RSD) of < 4%.
The growing number of highly potent APIs is also an issue for tablet-coating operations. “When highly potent tablet products are being coated, it is very important that not only the product quality be maintained, but the operators must be protected as well. That need is leading to greater automation of all aspects of drug production, including tableting-coating processes,” notes Nigris.
Need for flexibility and uniformity
The greater need for uniformity and worker protection comes at a time when pharmaceutical companies are also looking for greater flexibility in their tablet coating processes in order to meet variable demand for their products. Traditionally, perforated coating pans have been used for tablet coating. Using a solid pan, however, according to Nigris, increases the drying efficiency and provides more flexibility. “Not only can a solid pan handle a greater range of product types, from pellets to microgranules to even powders, it can be operated at as low as 20% of the maximum capacity, which provides more flexibility with respect to production scale.”
Tablet beds with increased surface area have helped improve coating performance, according to Hack. “The increased surface area of tablet beds with elongated pans and reduced diameters enables the use of a larger number of spray nozzles for higher spray rates and, consequently, shorter process times combined with better distribution of the solution over the bed surface,” he observes. He adds that minimization of spray drying has also been achieved by changing the path of the airflow so that the air is directed straight into the bed, rather than across the spray zone.
The potential of PAT
The use of process analytical technology (PAT) also has the potential to improve the performance of tablet-coating equipment. “While true online process control is still in its infancy, it is enabling technology that will lead to advances in tablet-coating processes. At LB Bohle, therefore, we have conducted trials with the University of Dusseldorf with respect to the use of Raman spectroscopy for the online measurement of film coat thickness with good success. We are now striving to implement this capability as an option in our coating line,” Hack says.
While progress is being made, real implementation of online PAT is still a challenge, though. The implementation of effective continuous processes is also a need in the pharmaceutical industry. “Current continuous coaters provide processes with very high RSDs as measured by weight gain, and thus are ineffective in ethical formulations because they have a high rate of over-coating,” notes Hack. He adds that LB Bohle is striving to deliver a continuous coating process that can be used for both cosmetic and functional applications.
Despite recent improvements in flexibility and cleanability, Nigris believes these two issues still require further advancements. “Pharmaceutical customers want tablet-coating systems that are easy to clean and easy to validate. Movement towards less-perforated pans is helping to address this need. A solid surface is much easier to clean.”
Nigris also points to the increased automation of tableting coating equipment as being important for further advancement of coating technology. “Automated humidity controls are having a positive impact today. In the future, fully automated systems, including in terms of product handling, will go a long way to increase the ability for tablet-coating equipment to effectively interface with both upstream and downstream processing for automated loading and unloading.”
To that end, LB Bohle is partnering with both customers in the pharmaceutical industry and with universities to develop a new technology center on its main campus in Ennigerloh, Germany that will focus on a complete continuous process line that incorporates the latest technologies for dispensing, granulation, drying, compression, and coating, with an emphasis on PAT for each stage, according to Hack.
Meanwhile, Nicomac has focused its efforts on the development of a solid, nonperforated pan that can be used for process development and optimization as well as commercial production. “Having such flexibility in the production scale is a real advantage for smaller companies that can’t afford to purchase separate tablet-coating equipment for their R&D and production groups,” Nicos states. The company also believes that mega pans for the production of up to 2 tons can be an alternative to continuous coating operations using a series of standard pans.