Teva Pharmaceuticals [NYSE: TEVA]

Steve Brown

Pharmaceutical tablet coating was initially developed from the confectionary industry and transferred to the pharmaceutical industry to produce sugar coated tablets. These tablets are elegant and easy to swallow with the taste and odor of the active ingredient masked. This process was very effective but required long process times of upto 5 days and highly skilled operators. In the 1950s and 60s compression coating, also known as a tablet in a tablet, was developed as a replacement to sugar coating but due to complex tabletting machines and slow compression speeds this technology did not take off. In parallel, the advancement in soluble cellulosic polymers and the development of Pellegrini and side-vented coating pans soon became the standard for modern tablet film coating technology and replaced the traditional sugar coating process.

The first commercially available film-coated tablet was developed and introduced by Abbott Laboratories in 1954. This was produced from a hydroxypropyl methyl cellulose polymer dissolved in organic solvent and sprayed onto the tablets using a Wurster fluid bed process. The principle of spraying a coating solution or suspension onto a tablet which is then rapidly dried and repeated until the desired coating appearance or functionality has been achieved is still the same now as it was in 1954. The processing equipment evolved from the Wurster fluid bed process to the side vented coating pan, which is significantly more efficient. The cellulosic polymers also advanced to be aqueous soluble removing the requirement for solvent handling systems. The science of film coating and the knowledge developed to understand this process has evolved and is now a well understood technology.

The tablet film coating process is often the last major step in the manufacturing process and therefore is critical to ensure consistency and reproducibility to avoid costly product write off. Tablet film coating is a thermodynamically driven process and has been modelled by several researchers. It is also a complex process with many input variables that can impact the product quality and process efficiency. In development it is important to ensure the tablet shape has been optimised for tablet coating to prevent twinning, edge chipping and embossing erosion. The coating formulation must be compatible with the active substance and the excipients to prevent degradation. There must be good coating to tablet adhesion, but also flexibility to allow film relaxation and prevent the embossing bridging or cracks forming in the coating. The process must be developed to ensure an even and elegant coating by optimising the drum rotation speed, spraying parameters and air flow. To ensure a highly robust and efficient process the drying air should be conditioned to a set dew point and the process variables monitored and closely controlled, ideally by an automated system.

Advancements in immediate release tablet coating have been in the development of new polymers and coating formulations for tablet coating that give higher coating efficiency and application rates as well as added functional benefits. The first improvement to the immediate release HPMC based coating formulations was the addition of lactose or other soluble sugar, this gave the benefit of increasing the solids content of the spray solution without increasing viscosity above the sprayable limit. 

A reduction in coating time by 40% is the typical improvement expected and the addition of the sugar also enhanced adhesion to the tablet. The second major advancement was the use of Poly Vinyl Alcohol as the film forming polymer, the solids content of the spraying suspension could be increased to approximately 25-30% with a further reduction in coating time. The PVA coatings also have excellent adhesion and film strength, with the additional benefit of a low coefficient of friction that enables faster packaging operations. Other polymers and coating systems have been developed that ease swallowing, enhance gloss of the tablets, further increase coating efficiency and speed. For functional coating there is a large range of different polymers with pH sensitivity, semi-permeable membranes and moisture barriers available.

Functional coatings that control the release of the drug from the tablet pose a particular challenge due to the more precise coating thickness requirements to give consistent release profiles. The coating polymer material specification also needs to be defined so that the functional properties of the materials give the target dissolution profile across the specification range. An alternate approach is to modify the process within validated ranges to accommodate the variation in these polymer materials. In these cases the criticality of process control and monitoring to control the process efficiency are essential to maintaining a process with a good capability.

The advancements in tablet coating equipment is the development of semi-continuous or continuous coating machines. These machines have been developed for either high volume rapid coating with the continuous coaters from O’Hara FCC500, Thomas Engineering Flex CTC and coaters matched to the output of continuous granulation and tableting lines like the Bohle KOCO and DRIACONTI-T and GEA ConsiGma coater. With these advances in technology the application of Process Analytical Technology to monitor the film coating process have also been developed. Near-infrared, Raman and Terahertz PAT tools have been applied to monitoring coating in real time and can show the consistency and coating thickness applied. Real time monitoring in combination with advanced automated process control can be used to ensure the product quality across longer production runs and support a real time release control strategy.

Tablet coating has evolved over the decades to be an advanced process which can produce an elegant highly consistent product in an efficient process with low cost. Continuous tablet coating is increasingly becoming the chosen technology due to its flexibility in batch size and enhanced process controls.