According to World Population Prospects 2019 (United Nations, 2019), by 2050, 1 in 6 people in the world will be over the age of 65, up from 1 in 11 in 2019. With the rise in the aging population, it has become absolutely necessary to optimise pharmaceutical formulations according to suit the needs of this population. Ageing is associated with an increasing incidence of chronic diseases and co-morbidities. Most elderly patients take many different medications for multiple conditions which makes compliance difficult. Reports indicate that patient adherence to therapies involving self-administration declines due to inconvenience caused by increase in complexity, frequency, and duration of the regimen.  

Greater attention and effort are required to develop patient centric pharmaceutical products for geriatric populations to address the diverse needs of this patient group. While defining the Quality Target Product Profile (QTPP) and selecting an appropriate dosage form, it is important to consider such patient requirements and how the product may be administered in addition to the technical feasibility of development and manufacturing processes. Although the oral route is considered the most preferred for being convenient, easy-to-administer, non-invasive, and allowing self-administration, it requires swallowing which in older patients can be impaired. Due to ageing and conditions like dysphagia, swallowing solid oral dosage forms effectively and safely in this population can be challenging.  

Enhancing swallowability  

Different factors such as physical attributes, dosage design and quality attributes of the solid oral dosage form impact its swallowability and oesophageal transit time. Physical parameters, such as tablet size, shape, and thickness are strongly associated to patience adherence and therefore can be considered as critical attributes for swallowability.  

It may be reasonable to reduce pill burden and encourage patient adherence by combining two or more doses in one. However, this will significantly increase the size of the dosage form and will be perceived as difficult to swallow by elderly patients. Therefore, the size of the dosage form is the most important physical attribute influencing swallowing safety. Increasing tablet or capsule size is also believed to correlate with increasing difficulty in oropharyngeal transfer.  Studies performed to understand the effect of shapes of dosage forms on swallowability have shown that flat-shaped tablets are more likely to adhere to the oesophagus as compared to convex-shaped tablets. Oval and oblong tablets on the other hand have shown faster oesophageal transit time as compared to round tablets with the same density. 

Dosage design and quality attributes like surface roughness (e.g., film coating), disintegration time, and propensity for swelling are other important parameters that impact swallowing performance. Several studies assessing the impact of tablet surfaces on swallowing experience show that coated tablets not only reduce the number of swallows but also the strength required to swallow, enhancing the swallowing experience. Swallowing uncoated tablets may require higher oesophageal contraction force.  Furthermore, when compared to smooth coated tablets, uncoated tablets with rough surfaces have increased transit time which in turn can increase the risk of sticking in the oesophagus. Solid oral dosage forms with smooth surface coatings can therefore considerably reduce cases of non-adherence to enhance swallowability. 

Dosage form 

Patient centric dosage forms that help enhance swallowing experience include chewable tablets, orally disintegrating tablets, minitablets and multiparticulate systems, which also allow for flexible dosing.  

Conventional dosage forms can also be made more patient-centric by coating their surfaces to enable easy swallowing. 

Ensuring safety of excipients 

With aging, reduction in liver perfusion and renal function are known to occur in the body. Therefore, accumulation of excipients in elderly patients may cause adverse effects that may lead to toxicity. The salt and electrolyte content of the dosage form need to be carefully evaluated since high levels of sodium or potassium may not be suitable for patients with renal insufficiency, and high salt intake can develop or aggravate hypertension in adults. Patients on sodium-containing formulations are at a higher risk of experiencing incidents of cardiovascular events compared to those on non-sodium formulations of the same drugs.  

Conclusion 

Regulatory agencies like the European Medicines Agency (EMA) strongly encourage integrating a patient-centric approach to design and develop pharmaceutical products. The ‘Reflection paper on the pharmaceutical development of medicines for use in the older population’ published by EMA also mentions several other product characteristics that can influence patient acceptability besides the ones discussed above such as recommended dosing frequency, duration of treatment, instructions on moments of dosing, authorised shelf-life and recommended storage conditions, handling to be conducted prior to use, the container closure system, complexity of the dosing instructions, readability of the package leaflet and so on. Collecting relevant data from clinical trials, representative simulated use studies, human factor studies with healthy volunteers or patients, market experiences can greatly help understand patient acceptability better. 

References  

1. Drumond N, Stegemann S. Better Medicines for Older Patients: Considerations between Patient Characteristics and Solid Oral Dosage Form Designs to Improve Swallowing Experience. Pharmaceutics. 2021; 13(1):32. https://doi.org/10.3390/pharmaceutics13010032  

2. Walsh J, Ranmal SR, Ernest TB, Liu F. Patient acceptability, safety and access: A balancing act for selecting age-appropriate oral dosage forms for paediatric and geriatric populations. Int J Pharm. 2018;536(2):547-562. doi:10.1016/j.ijpharm.2017.07.017 

3. US FDA Guidance for Industry: Size, Shape, and Other Physical Attributes of Generic Tablets and Capsules; June 2015 Size, Shape, and Other Physical Attributes of Generic Tablets and Capsules Guidance for Industry (fda.gov)

4. European Medicines Agency. Reflection Paper on the Pharmaceutical Development of Medicines for Use in the Older Population; EMA/CHMP/QWP/292439/2017  https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-pharmaceutical-development-medicines-use-older-population-first-version_en.pdf