How empowered do patients feel when it comes to the design of the drugs they take every day? It’s an impossible question to answer with absolute certainty, but one metric that helps to answer this question is medication compliance rates. In the U.S. alone, it’s estimated that drug non-adherance accounts for half of all treatment failures, with contributing factors ranging from inconvenient delivery forms, to unpleasant sensory profiles, complex dosing requirements or just plain pill fatigue.
Whether this disconnect stems from the multi-dose demands of chronic disease management or lack of access to tailored dosage forms, the responsibility lies with pharmaceutical manufacturers to understand and internalize patient experiences and adapt formulations in line with what users actually want and need. Achieving this will mean making a shift: A patient-centric development strategy that takes full advantage of advanced excipients during formulation design and can help to improve compliance rates.
In this article, we will explore three instances in which drug producers put patient experience front and center and what these examples can tell us about the essential role of excipients in making medications easier to swallow (both literally and figuratively).
Adapting Dosage Forms for Pediatric Compliance
Until as recently as the 1980s, the consensus was that clinical testing on child subjects was simply too hazardous, even if this meant very few drugs were explicitly approved for use by the youngest patients. In the absence of official pediatric medicines, responsibility for prescribing appropriate doses of adult medications was deferred to doctors.
This ‘off-label’ approach was usually successful thanks to the care and expertise of clinicians, but since the implementation of directives like the Best Pharmaceuticals for Children Act (2002) and the Pediatric Research Equity Act (2003), clinical standards have undergone a marked shift. Today, it’s widely recognized that children’s unique physiology requires tailored treatment, giving rise to dosage forms such as easy-swallow mini-tablets, dissolvable powder sachets and even medicated gummies.
From birth until late adolescence, children prefer highly sweet flavors and are far more sensitive than adults to bitterness. The masking of unpleasant-tasting active pharmaceutical ingredients (APIs) is therefore even more crucial for ensuring patient compliance in pediatric drug design.
The issue of acceptability becomes even more pressing in the field of pediatric oncology. Various forms of cancer treatment can leave young patients immunocompromised and more susceptible to infection, particularly in a busy hospital setting. To help protect young cancer patients, doctors often prescribe the antibiotics sulfamethoxazole (SMX) and trimethoprim (TMP) which, while effective, can be difficult for children to swallow in pill form or too unpleasant-tasting to take as a liquid suspension.
Our first example of smart, patient-centric reformulation revolves around these two bitter drugs as researchers set out to create palatable and — crucially — personalized chewable tablets via semi-solid extrusion (SSE) 3D printing. In their recently published paper detailing the project, authors Stoops et al. describe their development of three specialized “pharma-inks” (mixtures optimized for SSE 3D printing that contained SMX and TMP), alongside binding, taste-masking and sweetening excipients including mannitol, pregelatinized starch, gelatin and sucralose. Over the course of a three-month, in-hospital study, it was demonstrated that both the pharma-inks and the final 3D-printed chewable tablets showed good stability over time (when left at room temperature and refrigerated), and achieved equivalent dissolution profiles to those of commercially available SMX and TMP formulations.
Most importantly, human sensory evaluations confirmed that this new formulation significantly improved palatability, with far lower bitterness perception to traditional suspensions. The formulation also offered the added advantage of precise, customizable dosing thanks to the print-on-demand manufacturing method. While further refinement is needed to improve the chewable tablets’ texture, these results convincingly demonstrate how a patient-centric approach to dosage design not only improves compliance, but can also lessen the discomfort of young patients already experiencing serious health challenges.
Excipients’ Role in Alleviating Drug Side Effects
As we have seen, rendering APIs palatable is vital to patient compliance. In some cases, such as clarithromycin — a commonly used antibiotic — the intensely bitter flavor has been known to induce nausea or even vomiting upon ingestion.The side effects here are triggered by sensory properties rather than the mechanism of the API, but the result is still poor patient compliance and possible avoidance of the drug product for future treatments. Drug developers and clinicians have investigated several methods for overcoming clarithromycin’s extreme unpalatability, such as the development of transdermal patches, and orally dispersible tablets (ODTs) that allow for smaller doses of an API to be absorbed before reaching the stomach, lessening the risk of gasterointestinal symptoms. With the help of a multifaceted class of excipients however, the oral administration route can be made not just viable, but preferable.
Cyclodextrins are a family of naturally derived, ring-shaped molecules made from glucose units. Their unique structure features a hydrophobic inner cavity and a hydrophilic outer surface, which allows them to form inclusion complexes by trapping hydrophobic molecules within their internal cavity. When complexed with clarithromycin, cyclodextrins like hydroxypropyl-β-cyclodextrin (HPβCD) effectively encapsulate the bitter molecules, preventing their interaction with taste receptors in the mouth upon administration.
By physically sequestering the API in this way, HPβCD significantly masks the drug’s inherent bitterness, thereby alleviating the immediate side effects of gagging, nausea and vomiting. With complexation providing a highly effective foundation, formulators can then harness more traditional taste-masking excipients such as mannitol- or xylitol-based coatings to take tablets from merely tolerable to actually pleasant.
Reducing Dosing Frequency for Improved Patient Experience
In the previous sections, we have discussed the importance of how patients experience their medications, but an equally vital consideration is how often. The vast majority of medications prescribed to patients around the world fall into the immediate-release category, where the objective is to deliver the API as quickly as possible. Based on the clinical dose of the API, sometimes the dosing regimen calls for administration of multiple doses (more than one dose at a time) at multiple points (bi-daily, tri-daily, etc.), leading to pill fatigue. Drugs with this type of dosing regimen may be acceptable for the treatment of acute or short-term conditions, but for chronic disease, the burden of taking multiple doses each day (for longer time periods) can quickly lead to pill fatigue.
Dosage form designs using modified, delayed or controlled-release technologies are a highly effective strategy for improving patient compliance by reducing the frequency and number of daily doses. An apt example of the benefits reformulating for extended release can be found in the widely used type 2 diabetes medication, metformin. This drug forms the cornerstone of diabetes management by helping to control patients’ blood sugar levels, but in the process, it often produces uncomfortable gastrointestinal side effects. In response, drug developers began experimenting with extended-release formulations of metformin that allow for once-a-day dosing compared to the multiple administrations required with immediate-release varieties. This removes a significant part of the daily pill burden, while providing a more consistent release of the drug into the bloodstream, thereby enhancing patient convenience and comfort.
This, and the other case studies included above, demonstrate that many of the most effective routes to more patient-centric drug design are paved with advanced excipients. This is no different in the case of modified-release medications, where polymeric excipients like hydroxypropyl methylcellulose (HPMC) actuate the delayed release of the API by forming a gel-like hydrophilic matrix when it encounters the aqueous environment of the GI tract. Though it is used for its extended-release applications, HPMC also exhibits poor flowability and tabletability. To overcome this challenge, formulators can turn to co-processing HPMC with mannitol (which is a sweet, stable and highly compressible excipient). This ensures a solution that offers the unmatched diffusion properties of HPMC, along with good processing properties of mannitol.
Dosage form designs using modified, delayed or controlled-release technologies are a highly effective strategy for improving patient compliance by reducing the frequency and number of daily doses.
A New Era of Patient Centricity as Standard
More than an ambition or just another formulation strategy, patient-centric drug design is the future of pharma. As emerging technologies make gathering and implementing user feedback simpler than ever, historical barriers to progress are falling away to reveal new vistas of opportunity. As we’ve seen, the thoughtful application of modified dosing, tailored delivery methods and advanced excipients can be transformational in overcoming medication nonadherence and crafting solutions that are not only therapeutically effective, but easy for patients from compliance perspective.
With these technical advancements, we can look forward to a future where compliance rates are high and patient-centric design is simply the norm, making users feel seen, heard and empowered in the process.
References
Kim, J. et. al. (2018, Jan). Medication Adherence: The Elephant in the Room. US Pharm. 43(1), 30-34.
State of Paediatric Medicines in the EU. (2017). [Report from the Commission to the European Parliament and the Council]
Christensen, M.L. (2012, April). Best pharmaceuticals for children act and pediatric research equity act: time for permanent status. J Pediatr Pharmacol Therapy. 17(2), 140-1.
Mennella, J. and Bobowski, N. (2015, Dec). The sweetness and bitterness of childhood: Insights from basic research on taste preferences. Physiology & Behavior. 152(B), 502-507.
Stoops, M. et. al. (2025, May). Clinical implementation of a paediatric 3D-printed combination of Sulfamethoxazole and Trimethoprim. International Journal of Pharmaceutics. 676,125581.
Alkilani, A., et. al. (2023, Jan). Preparation and Characterization of Patch Loaded with Clarithromycin Nanovesicles for Transdermal Drug Delivery. J. Funct. Biomater. 14(2), 57.
Malkawi, W. et. al. (2022, April). Formulation Challenges and Strategies to Develop Pediatric Dosage Forms. Children. 9(4), 488.
Jansook, P., et. al. (2018. Jan). Cyclodextrins: structure, physicochemical properties and pharmaceutical applications. International journal of pharmaceutics. 535(1-2), 272-284.
Wheless JW, Phelps SJ. A Clinician’s Guide to Oral Extended-Release Drug Delivery Systems in Epilepsy. J Pediatr Pharmacol Ther. 23(4):277-292.
Roy, E. (2022, Feb). Pill Fatigue. Keppel Health Review.
Hanefeld, M. and Drzewoski, J. (2022, Feb). The Current and Potential Therapeutic Use of Metformin—The Good Old Drug. Pharmaceuticals. 14(2), 122.
Bonnet, F. and Scheen, A. (2017, Dec). Understanding and overcoming metformin gastrointestinal intolerance. Diabetes. 19(4), 473-481