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EMA and FDA guidance encourages design of drug products to improve patient compliance.
Patients prefer tablet dosage forms because they look familiar, and tablets are usually coated, making them easy to recognize and simple to take. The disconcerting news, however, is that in a survey of US adults, 4 in 10 reported difficulty in swallowing tablets, negatively affecting patient compliance. Of those 40% with difficulties, 14% delayed taking a dose, 8% skipped a dose, and 4% discontinued the medication altogether (1). Data like these have not escaped the attention of major regulatory agencies, including FDA and the European Medicines Agency (EMA).
Within the past three years, FDA issued two separate guidance documents that encourage drug formulators to design drug products with patient compliance and the reduction of medication errors in mind (2, 3). Commonly referred to in the United States as “safety by design” (SbD), the concepts outlined by FDA reference tablets that should be of an appropriate size, shape, and coating to enhance swallowability and palatability of the drug.
In a guidance document, FDA noted that “coating can potentially affect the ease of swallowing tablets or capsules. The lack of a film coating can decrease or prevent tablet mobility compared with a coated tablet of the same size and shape” (2). Logic dictates that if a dosage has the potential to be a choking hazard, then coating should be considered to aid the patient’s ability to swallow and avoid the risk of the patient not taking their medication. This guidance from FDA was applicable to all new drug applications (NDAs) as well as abbreviated new drug applications (ANDA) and over-the-counter monograph drugs.
FDA suggested that generic-drug manufacturers should also ensure that the design of a generic version should not hinder patient compliance. Manufacturers should “consider the size, coating, and palatability of oral products. A drug product can become a choking hazard due to the size of the tablet or capsule. If the tablet or capsule coating is too sticky, it can become lodged in the patient’s throat or gastrointestinal tract” (3). The guidance also recommends more attention to dosage shape and size, encouraging manufacturers to reduce cross-sectional areas of larger tablets to improve swallowing. The guidance concludes that “tablet coating, weight, surface area, disintegration time, palatability, and propensity for swelling should also be considered when designing oral products to avoid medication errors related to swallowability and patient compliance” (3).
Patient safety concerns are also being addressed by European regulators. In November 2015, EMA issued a comprehensive guide on minimizing risk for patients, which lists concerns for elderly patients who “may face physical and cognitive impairment, and hence, they may have difficulties in taking their medicines (e.g., swallowing tablets, opening packaging, or reading their user instruction and package leaflet). The pharmaceutical development of medicines for use by older patients should take such aspects into consideration” (4).
Focus on the elderly population continues to be addressed with a reflection paper issued by EMA in 2017 on pharmaceutical development of medicines for use in the older population, especially to address tablet mobility (5). This paper discusses the particular problems that elderly populations face and cites that “elderly patients are more likely to experience conditions which lead to impaired swallowing, such as stroke or Parkinson’s disease. This can lead to accidental under dosing, which can be managed appropriately by the development and use of formulations which are easier for such patients to swallow” (5).
Tablets are now being presented as specialized dosage forms: medicines that deliver complex treatments including drug combinations, layered tablets, and modified release forms, for which it is even more important that the patient follows an exact dosing regimen. However, many of these newer dosage forms are presented as larger tablets, which reduces the frequency of dosing but may present issues with swallowing and tablet mobility. The importance of good tablet design to address patient acceptability and compliance is paramount, and addressing this need will help to satisfy regulatory concerns also. The fact that regulators and industry are now actively addressing this topic is good news for patients and caregivers.
1. Harris Interactive Inc., Pill-Swallowing Problems in America: A National Survey of Adults (Harris Interactive Inc. for Schwarz Pharma, New York, NY, 2003).
2. FDA, Guidance for Industry: Safety Considerations for Product Design to Reduce Medication Errors (Silver Spring, MD, April 2016).
3. FDA, Guidance for Industry: Size, Shape, and Other Physical Attributes of Generic Tablets and Capsules (Silver Spring, MD, June, 2015).
4. EMA, Good Practice Guide on Risk Minimisation and Prevention of Medication Errors (London, Nov. 18, 2015).
5. EMA, Reflection Paper on the Pharmaceutical Development of Medicines for Use in the Older Population (London, May 18, 2017).
Vol. 41, No. 10
When referring to this article, please cite it as R. Steffenino, "Is Your Tablet Hard to Swallow? Guidance Addresses Drug Tablet Design," Pharmaceutical Technology 41 (10) 2017.
Rita M. Steffenino is manager, Brand Enhancement and Marketing Programs at Colorcon.