Coating compliance — looking at the important considerations when coating tablets
Jason Teckoe, technical director, Colorcon EMEA, discusses the important considerations when coating oral solid dosage forms.
Tablets remain the most common solid oral dosage form for many reasons, including ease of manufacture, convenience for the patient, accurate dose administration and good stability. Good tablet design can be used to provide product differentiation, avoid medication mix-ups and deter counterfeiting. It can also impact patient compliance.
So, what are the reasons for including a coating on an oral solid dosage form? Purely from an aesthetic point of view, uncoated tablets are undistinguished. In addition, a rough-looking tablet can appear to be of poor quality; not an attribute you want, especially in a medicine.
From the patient’s perspective, coating makes the tablet appear easier to swallow and aids in visual differentiation, thus reducing the potential risk of medication errors. Coating also reduces tablet friability and overcomes any damage or dusting issues often associated with uncoated tablets.
From a manufacturer’s perspective, the coating helps to protect the tablet, provide a desired release profile, mask the taste of a bitter drug, minimise the impact that environmental conditions may have on drug stability, extend the product shelf life, aid packaging and help differentiate the product.
Recent focus on medication errors has led regulatory bodies to consider tablet differentiation more prominently, encouraging manufacturers to think more about the patient’s perspective and whether they are likely to follow the recommended dosing regimen outlined in their prescription.
The FDA, for example, has released two industry guidance documents on this topic,1,2 intended to champion the patient’s perspective, improve patient compliance and medication outcomes. Adding a coating to a previously uncoated tablet would improve patient compliance and bring the tablet in line with the FDA’s recent recommendations.
Considering coatings
When beginning a project that involves a coating system, it’s vital to discern which considerations are important for your product. Selecting the right coating, however, can be surprisingly tricky, and getting it ‘wrong’ can impact patient compliance or even compromise drug efficacy by negatively affecting the drug release profile.
The core is key:
The tablet core is key, as it’s the substrate the coating will be applied to; so, starting with a suitable surface is critical to achieving a good finished product appearance.
In solid oral dose development, compatibility of the active pharmaceutical ingredient (API) will drive the selection of the excipients. Excipient choices for a formulation are typically driven by functionality requirements and compatibility with the API.
The choice of coating depends on the chemical properties and chemical nature of the tablet’s core ingredients, including the API or where it needs to be released in the body, sensitivity to the environment, and the physical properties of the API. Every drug is different so there is not a ‘one-size-fits-all’ coating.
API sensitivity:
When coating an API that is moisture and/or temperature sensitive this presents physical challenges to overcome. To assist with these challenges, Colorcon offers specialist coatings such as Opadry QX that can be applied at high solids and low coating bed temperatures; whilst Opadry amb II, which provides moisture barrier properties, and is less prone to generating reactive impurities during accelerated storage conditions.
Coatings with a pH dependent release profile (enteric coatings) are typically used when a drug is acid labile, irritating to the stomach, or requiring targeted release in the small intestine for optimal bioavailability. These coatings employ the use of a pH-dependent polymer such as a methacrylic acid copolymer, which is designed to remain intact and protect the tablet or multiparticulate dosage form in the lower pH of the stomach and dissolve immediately in the elevated pH of the small intestine.
Acetylsalycylic acid (Aspirin) tablets and proton-pump inhibitors (PPI) such as omeprazole, use an enteric coating like Colorcon’s Acryl-EZE, aqueous enteric coating system, to protect the patient from the drug and vice versa in the low pH conditions of the stomach.
In addition to the coating composition, the coating process parameters are also important. Ensuring good mixing and physical movement of tablets in the coating pan and optimizing the thermodynamics of drying for the product all play a significant role in achieving a high quality, uniform tablet appearance with the desired functionality.
Special requirements:
The paediatric and geriatric groups are specialized patient groups that have unique requirements related to product performance and differentiation.
For paediatrics, taste-masking and the ability to swallow medications is important, so liquid dosing, mini-tablets or multi-particulates are often used, as they provide easier to swallow dosages and allow for dose adjustment based on patient age and size.
In addition to dosing and taste-mask properties, manufacturers also need to ensure their coatings are safe for use in the paediatric population. They need to confirm the raw materials contained in the product are suitable and ideally have existing precedence-of-use in a relevant paediatric application.
Meanwhile, the growing number of elderly patients, with inherent polymedication challenges, points to a need for increased product differentiation based on size, shape and colour of tablets, to enable patients, or their caregivers, to know they have taken the correct medicine at the right time.
Odour masking:
Some tablets also have a surprisingly bad odour, which can have a negative effect on patient compliance. If the patient has a poor impression of their medicine the moment they take it out of the packaging, it could be destined for failure.
Moreover, if patients get beyond the aesthetics and the smell, they often find that uncoated tablets are more difficult to swallow, as they can get stuck in the throat and start to disintegrate the moment they are exposed to moisture.
Continuous processing
Continuous processing is a growing trend in the pharma industry and being encouraged by regulatory agencies. This is not a new technology, but it is a new mindset for the pharmaceutical industry moving away from traditional batch processes.
The end goal of using continuous processes is not necessarily about achieving high volume throughput, but about adopting lean and consistent manufacturing processes that build quality into the manufacture of the product, rather than testing at the end of the process. One attribute that all continuous coating processes offer, compared to batch processing, is faster and more frequent presentation of tablets to the coating spray zone; this results in shorter cycle times to achieve consistent coating coverage. Creating an efficient continuous coating process not only depends on the equipment used, but also on the formulation of the coating.
A wide choice of film coatings is available, based either on hypromellose (HPMC) or more recently polyvinyl alcohol (PVA) polymers and the choice will depend on the specific needs of the application.
Generally speaking, most film coatings can be used in continuous equipment, but some provide better results than others, with each having its own advantages and challenges. HPMC systems have a higher comparative viscosity, which leads to a lower percentage of coating solids, around 12 to 15%. This reduces throughput rates and results in a narrower working window in terms of process parameters such as airflow and inlet temperature. PVA-based coatings which are used at around 20% solids, overcome this limitation and tend to work better at higher temperatures and airflows; both systems therefore provide challenges to attain optimal results for all tablets.
To meet the industry’s need for faster and more flexible coatings, especially for continuous manufacturing, Colorcon’s Opadry QX, quick and flexible film coating, allows for a higher percentage of solids (up to 35%) and results in a smooth, uniform tablet appearance. But perhaps the most significant advance this coating offers is the manufacturing flexibility, as it works well with all equipment types across a wide range of process conditions. This is especially important as companies may move product between different manufacturing locations and equipment types can vary between sites.
A more palatable dose
There are a few ways to try and make an uncoated tablet more palatable (e.g., adding colour, taste-masking ingredients or changing the shape to aid swallowing) but by far the simplest and most effective way is to add a film coating.
When considering coating an oral solid dosage form, try to remember the key aspects of the product’s core composition and how the coating can support and protect it while also creating an aesthetically pleasing tablet. Probably, and most critically, think about the patient who will definitely appreciate a pill that is easy to swallow!
References