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Elizabeth Shen, PhD, is technical marketing manager at Colorcon, Inc.
Materials and equipment innovations have advanced tablet coating from sugar to copolymers and simplified pharma production.
Advances in film coatings for pharmaceutical products have picked up the pace within the past 10 years with introduction of new technologies to support product stability improvements and increase process efficiency. The benefits are many; chief among them enabling manufacturers to simplify the progression from lab scale to full-scale production utilizing existing equipment, even when operating in challenging heat and humidity environments around the world.
Coating pills and tablets has been going on since the 1600s in the form of sugar coating to improve their robustness, stability, taste masking, and swallowability (1). Surprisingly, the original process continues today. While sugar-coating ingredients and processes are simple, skilled operators are required to judge when a batch needs additional sugar. Specialized handling of organic solvent materials is needed to apply the initial sub-coat. The process takes days and sometimes weeks to complete, with sealing, bulking, coloring, and final polishing of sugar-coated tablets (2).
With the introduction of polymer-based film coating in the 1950s, coating cycle times were cut from days to hours. With the new film coating process, a polymer solution is continuously sprayed onto the tablets resulting in a thin, uniform film coat (approximately 30 µm), providing numerous benefits including added tablet strength, improved bulk flow, easier swallowing, and improved aesthetics for product differentiation. The industry, however, was not quick to adopt this new process as organic solvents were still required and capital investment in perforated coating pan equipment was necessary (3).
Early film coatings were prepared in-house by the pharmaceutical manufacturers that sourced, tested, and combined the multiple components most often into hydroalcoholic systems. The coating ingredients were generally comprised of polymer, plasticizer, and pigment. Each ingredient could vary from batch to batch and required special preparation steps including high shear mixing and/or de-aerating. Maintaining color consistency from batch to batch-neither a specialty nor priority of pharmaceutical industry-presented another challenge. Combining these factors, it is easy to understand why early adoption of film coatings was a challenge.
As coating equipment improved, so did the film coating formulations and processes, moving from hydroalcoholic systems to fully aqueous processes. These coating systems were designed ready for use, with all ingredients selected and the color matched to meet individual specifications, removing the complexity of in-house development, material sourcing, and quality control. The prepared formulations were developed for ease of use: a single blended dry powder is added to water and the dispersion is ready for coating a short time later. Colorcon introduced the first fully formulated film coating system, an opaque dry dispersion, under the tradename Opadry in 1985 (4).
Hypromellose (HPMC) and other cellulosic polymers were included as the film forming agent for the early coating applications, and HPMC is prevalent today, mostly through precedence for use, rather than technical superiority. This polymer offers excellent film strength, but can result in finished product defects like peeling and logo bridging due to poor adhesion and elasticity. HPMC viscosity increases exponentially, limiting solids content of dispersions to 10-15% (w/w).
Later in the 1980s, coating innovations were introduced to improve productivity by inclusion of polysaccharides to the film coating formulation, resulting in a decrease of overall viscosity for the coating dispersion, resulting in faster application (5). These formulations also have limitations, with weaker films and a tendency for chipping on friable tablet cores.
The tempo started to pick up in the 1990s, with the exploration of non-cellulosic polymers such as polyvinyl alcohol (PVA) for film coating application. PVA provides a significant barrier to moisture and can also be coated at cooler and warmer temperatures than HPMC. Other advantages for PVA in film coatings include superior adhesion and lower viscosity compared to HPMC systems. Solids content could be increased to 20% for PVA systems, allowing for quicker process cycle times. The high adhesion, however, comes with a challenging tackiness that caused substantial sticking between tablets at higher spray rates. With clever formulation of the coating system, tackiness can be minimized to prevent defects and maximize coating productivity with PVA systems.
From a regulatory standpoint, PVA ran into some hurdles as it was not broadly acceptable. However, seeing the obvious technical advantages over existing HPMC-based coatings, Colorcon obtained several patents for PVA-based film coatings (6), and the path cleared for introduction to the market when generally-recognized-as-safe status was granted for PVA in 2003.
Most recently, polyvinyl alcohol-polyethylene glycol (PVA-PEG) graft copolymer has been recognized as a material with exceptional film coating properties. This polymer provides extremely low viscosity at high solids content (upwards of 30% solids), which allows for unparalleled productivity and maintains a smooth coating surface.
The productivity of PVA-PEG coatings allows manufacturers to break previous bottlenecks in the coating processes. Coating was often seen as the rate-limiting step in solid dose manufacturing; unmatched productivity allows for higher coating throughputs in batch and continuous processing (7,8).
1. J.A. Seitz, S.P. Mehta, and J.L.Yeager, Chapter 12: Tablet Coating; in The Theory and Practice of Industrial Pharmacy, 3rd Edition (Lea & Febiger, Philadelphia, 1986).
2. A. Barkley, S. Levine, and C. Signorino, Tablets and Capsules 4 (4) (2006).
3. S. Porter, “Coating of Pharmaceutical Dosage Forms” in A. Gennaro (Ed.), Remington: The Science and Practice of Pharmacy (895-896) (Lippincott Williams & Wilkins, Philadelphia, 2002).
4. A. Siahboomi, Pharm. Tech., 26 (8) (2014).
5. A. Rajabi-Siahboomi and T. P. Farrell, “Applications of Formulated Systems for the Aqueous Film Coating of Pharmaceutical Solid Oral Dosage Forms” in L. Felton (Ed.), Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms, Fourth Edition Volume 215 (CRC Press, Boca Raton, FL, 2016).
6. M.P. Jordan and J. Taylor, “Film coatings and film compositions based on polyvinyl alcohol,” U.S. Patent #6,448,323 B1, issued Sept. 10, 2002.
7. C. Cunningham, J. Cronlein, and O. Nohynek, Tablets and Capsules 13 (10) (2015).
8. J. Teckoe and C. Cunningham, The Medicine Maker 44-45, (October 2016).
Vol. 41, No. 7
When referring to this article, please cite it as E. Shen, “Coatings Sweeten Pharma Tablet Production,” Pharmaceutical Technology 41 (7) 2017.