Use of high solids tablet coatings has steadily increased in line with stricter restrictions on solvent use. Dr Stuart Porter, senior director of pharmaceutical r&d at International Specialty Products in the US, reviews the progress of film coating technology and future challenges
Sugar coatings were introduced as a pharmaceutical coating technique more than 100 years ago, and up until the 1960s they were still the predominant method of masking taste and providing an elegant finish. Despite the time-consuming process, sugar coatings are still in use today, although to a more limited extent.
By the early 1970s, pharmaceutical manufacturers had adopted film coating, using organic solvents and coating formulations based on cellulose ether polymers such as methylcellulose (MC), ethylcellulose (EC), hydroxypropyl methylcellulose (hypromellose, HPMC) and hydroxy propyl cellulose (HPC), as an alternative means of coating pharmaceutical oral solid dosage forms. Film coatings could be applied in a few hours resulting in considerable time and cost savings compared with a traditional sugar-coating process.
With these process benefits, film-coated tablets became more common; the reliance on the use of organic solvents was still, however, an impediment to the widespread interest in producing coated tablets. But all that changed with the introduction of aqueous film-coating processes that began in the late 1970s.
At that time, growing concerns with air quality led to new regulations on solvent emissions. As a result, the industry looked to move from organic solvent-based coatings to aqueous coatings, something that was facilitated by the introduction of two processing technologies, namely the Wurster fluid-bed process and the Accela-Cota side-vented pan process. These technologies, by essentially reducing reliance on conventional pan technology (with its mixing and drying limitations) paved the way to using water as the main vehicle for coatings.
Of course, the transition to aqueous coating was also facilitated by the fact that many of the film-coating polymers already in use were water soluble, with the only exceptions being polymers such as ethyl cellulose and certain acrylic copolymers that were traditionally used for modified-release applications. The subsequent development of "latex" coatings even facilitated the use of water-insoluble polymers in aqueous processes.
By the mid-1980s, aqueous film coating had become the primary process for coating pharmaceutical oral solid dosage forms. The availability of aqueous processes and several unfortunate events in the early 1980s that involved the tampering of oral dosage forms based on capsules, led to a rapid growth in interest in coated dosage forms during that decade. That interest has been maintained to this day.
Film coatings are applied as clear, white or coloured systems, and typically consist of a multiplicity of components (polymers, plasticisers, pigments, opacifiers, detackifiers, wetting agents) depending on the type of system being applied.
Traditionally, pharmaceutical companies prepared their own coating formulations by purchasing all of the ingredients separately. Coincidental with the rapid growth in film coating during the 1980s, ready-to-use coating systems (typically in dry powder form that allowed rapid reconstitution into water) were introduced to the pharmaceutical industry. These complete coating systems minimise the number of materials that a pharmaceutical company needs to keep in inventory, thus simplifying the QC process for material release and reducing the steps required to prepare the coatings suspension.
In addition, use of such coating systems allows the pharmaceutical scientist to take advantage of the film-coating formulation and processing experience offered by the vendor. Examples of some of these complete systems are Advantia (ISP), Opadry (Colorcon), Seppifilm (Seppic), and Spectrablend (Sensient).
While the fundamental aspects of film-coating technology have changed little over the past 20 years or so, incremental changes, both with respect to coating materials as well as coating processes have occurred. In terms of process technology, a major change that has taken place is the global availability of side-vented coating pans, often from regional vendors; this has facilitated the worldwide adoption of aqueous processing technology.
In addition, the introduction of continuous coating processes has dramatically increased productivity (with outputs in the range of 1,000 to 2,000kg/h) while minimising exposure of product to stressful process conditions that involve high temperature and humidity.
At the same time, the leading vendors of coating systems have striven to embrace new coating materials that facilitate the availability of coating formulations that can be applied at high solids, usually greater than 15% w/w in water and often greater than 20%. These high solids coating systems permit significant improvements in productivity, and adapt better to continuous processes. Figure 1 shows the extent of the reductions in process times that can be achieved (up to 40%) with a high solids coating system, such as Advantia Preferred HS coating (ISP), compared with a traditional HPMC-based coating system.
Often these new high solids systems utilise new polymers (at least in terms of those typically employed in coating formulations) and polymer combinations that provide other benefits, such as substantially increased film adhesion and improved barrier properties (with respect to environmental gases such as water vapour and oxygen), thus potentially improving the stability of the final coated products.
For example, recent studies by ISP (see table 1) compared the adhesion of a traditional HPMC-based film coating and a high solids film coating with a standard placebo core as well as an ibuprofen, a waxy material. The results show significant improvement in adhesion values for the high solids system.
Improved film adhesion is required when coating difficult-to-coat cores or to overcome logo bridging problems. The photographs in Figure 2 illustrate how a high solids coating system (Advantia Preferred HS, ISP) provides significantly better logo definition than the traditional HPMC-based coating system.
With the drive to high solid systems to increase productivity of the coating operation, it is important to maintain the elegant appearance associated with film-coated tablets. As high solids coating suspensions tend to dry faster (because there is less water to evaporate), there is the increased risk of producing tablets with a visually rougher film coating.
A comparison of surface roughness values for two high solids systems, a polyvinyl alcohol (PVA)-based coating and an Advantia Preferred HS coating (non-PVA system), is shown in Figure 3. The data indicate a consistently rougher tablet surface with the PVA-coating system over a range of processing conditions.
A visual inspection of tablets (Figure 4) when the film coatings were applied from a 20 % w/w coating suspension (spray rate - 12.5g/min; atomising air pressure - 15psi (1 bar)) shows significant differences between the film coating systems in terms of the surface elegance achieved, but also confirm that it is possible to coat tablets at high solids while maintaining good tablet appearance.
While there is no question that film-coating processes remain an integral part of the overall manufacturing processes for pharmaceutical oral solid-dosage forms, some key challenges that face advocates of this process include:
- Gaining a better understanding of the fundamentals of the process in order to address ongoing concerns (about that process) often raised by regulatory agencies.
- Implementing the tenets of the Quality by Design (QbD) initiatives being promulgated by regulatory agencies, especially for a process where such implementation is still a challenge.
- Utilising film coating as an effective means of dealing with issues of counterfeiting of pharmaceutical oral solid dosage forms.