Research suggests that medical non-adherence accounts for half of all treatment failures in the US, resulting in at least 100,000 preventable deaths each year.1 Widespread, systemic and deeply damaging to public health, this phenomenon is also extremely wasteful.
Current estimates put the cost of medical non-compliance at a staggering $100 billion per annum, which is equivalent to more than a third of the UK’s total healthcare expenditure for 2021.2,3
The gravity of this issue is obvious, but the healthcare industry is yet to reach a consensus on the best way to turn the tide.
Some health professionals see the medication non-adherence crisis as a “patient problem” to be solved at an individual level, rather than an issue that deserves sector-wide attention.4
At the opposite end of the spectrum, others see patient non-compliance as so all-encompassing — impacting everything from disease prevention and public mental health support to sustainability — that it’s hard to identify where and how interventions should be made.
In this article, we will explore one of the many potential frameworks available to tackle the epidemic of medical non-compliance, which takes the issue back to the medications themselves: how they are made, how they are administered and the ingredients they contain.
Read on as we explore the scope of the medical non-compliance epidemic and the excipient solutions that are helping the pharma industry to focus on the patient experience.
To take or not to take
Billions of people worldwide rely on daily prescriptions to stay healthy. It is estimated that 70% of the US population takes at least one medication every day; and, approximately half of all citizens throughout the EU member states self-reported the use of prescription medications in 2019.5,6
As eluded to already, though, a significant proportion of patients do not or cannot take these medicines as prescribed.7
There are almost as many explanations for poor medication compliance as there are patients, but some of the most widespread include
- inconvenient or unsuitable dosage forms
- pill fatigue or feeling overwhelmed by multiple daily doses
- medicines simply being unpleasant to take owing to bad taste, smell or texture.
These hurdles can apply to any medication user, but they present a particular problem for paediatric, geriatric, psychiatric or any other patient groups with specialised needs.
Ease of swallowing, for example, is a critical consideration for very young or old patients, as well as anyone suffering from dysphagia. Dosage is another fraught issue for these groups.
Often, doctors treating rare medical conditions in children are forced to prescribe half pill doses of adult medications owing to the lack of similar drugs tailored for paediatric consumption.
This not only makes following treatment plans more difficult for parents and children alike, but also means that halved pills are frequently stored outside of the blister pack, raising the risk of drug loss or instability.
As many of these barriers relate to the medications themselves, pharmaceutical manufacturers have a vital role to play in improving patient compliance. Active pharmaceutical ingredient (API) development tends to dominate discussions regarding what that role should be, but when the topic turns to the practicalities of drug delivery, excipients deserve an equal place in the spotlight.
Focus on formats
More than any other factor, delivery format has the biggest impact on the success or failure of any medication. The spirit of this sentiment dates back all the way to the “father of medicine” himself, with Hippocrates instructing physicians to “not only be prepared to do what is right […] but also to make the patient … co-operate”.8
In short, even the most advanced drug in history is functionally useless if patients don’t know how or don’t want to take it. The key responsibility for pharmaceutical producers, therefore, is to develop delivery formats that align with patient needs, particularly those with atypical requirements. This is when functional excipient solutions display their true potential.
From orally disintegrating tablets (ODTs) and films (ODFs) to minipills and effervescent medicines, multipurpose fillers, binders and diluents make alternative dosing routes possible. Take ODTs and ODFs as one example of how the right excipient formulation has radical implications for drug accessibility.
These delivery methods are designed to dissolve rapidly in the mouth on contact with saliva, making medications safer, easier and more convenient for patients with swallowing difficulties (including children and the elderly).
To ensure ODTs and ODFs dissolve successfully in the oral cavity, drug producers need excipients that exhibit a few key attributes: superior processability, mechanical strength, dispersibility and palatability.
Although each of these features is important in its own right, the critical consideration in dispersible formulations is balance. Consider for example the fact that an ODT excipient has to offer both binding and strengthening capabilities, as well as rapid disintegration. In these applications, therefore, multifunctionality is a must.
Manufacturers of ODTs and ODFs equally require excipient solutions that combine a pleasant flavour and texture.
Ticking all the boxes, Roquette’s PEARLITOL Flash mannitol-starch compound — a direct compression solution specifically developed for dispersible dosage forms — offers superior chemical inertness and a consistently rapid disintegration time, as well as a clean mild taste and texture.
With the judicious use of versatile excipients such as these, manufacturers can deliver medicines that are easy, convenient and even pleasant to take.
The problem with pill fatigue
Sometimes the main barrier to patient compliance is not the type of medication, but how often it needs to be administered. Many treatments, particularly those designed to manage chronic conditions, require multiple daily doses to be effective.
Complex medication regimens such as these can lead to “pill fatigue” in even the most fastidious patients — a phenomenon that can have serious consequences for dosage consistency and the success of treatment plans. Here again, functional excipients provide an answer by unlocking the potential of controlled-release dosage forms.
Otherwise known as extended-release formulations, these delivery formats combine a highly soluble BCS (Biopharmaceutical Classification System) Class I or Class III API with an excipient that’s capable of releasing the drug slowly during a number of hours.
The controlled release capacity of these medications allows for reduced dosing frequency and, with it, a lower risk of pill fatigue. What’s more, this delivery approach makes maintaining a consistent dosage level far simpler, curbing the fluctuations that can cause under or overdosing.
Modified release formulations require an excipient that’s capable of gradually diffusing the API — typically with a polymeric base. The best-known of these ingredients is hypromellose or hydroxypropyl methylcellulose (HPMC), a cellulosic compound that works by forming a gel-like hydrophilic matrix once in contact with the aqueous environment of the gastrointestinal (GI) tract.
For many years, wet granulation has been the only viable processing method for HPMC-based controlled release drug formats.
This has meant that, to take advantage of HPMC’s slow diffusion profile, drug manufacturers must contend with a complex, costly and time-consuming production process that requires careful management to produce successful results.
In light of these drawbacks, manufacturers are increasingly searching for solutions that combine the controlled release capabilities of HPMC with the improved process efficiency of direct compression excipients such as spray-dried (SD) mannitol.
Roquette recently addressed this demand with the launch of PEARLITOL CR-H, a blend of high-performance mannitol and hypromellose that’s designed for direct compression.
By unlocking the potential for reduced dosing frequencies alongside improved process efficiency, this solution helps brands to extend the benefits of controlled release delivery formats to the patients who need them most.
Taste is king
It may seem obvious, but taste is an incredibly important factor in oral drug delivery. A drug manufacturer can spend years crafting the most innovative dosage forms, but all that effort will mean little if the final product leaves a bad taste in patients’ mouths.
A good taste-masking excipient is therefore critical. Armed with these solutions, brands can make use of APIs that were previously unsuitable for oral dosage owing to a bitter flavour, differentiate their offering from any similar drugs on the market and — most importantly — deliver better health outcomes through improved compliance.
On a technical level, taste masking is typically achieved through one or a combination of three different approaches:
- chemically modifying the API into a salt or prodrug form to reduce its bitterness
- processing the API using methods such as molecular complexation or particle coating to shield bitter compounds
- applying a direct sweetening effect via pleasant-tasting excipients.
In the case of mildly bitter APIs, manufacturers can take the most straightforward step of adding flavours, acids or sweeteners. Mannitol-based excipients are often selected for this purpose thanks to their mild, naturally sweet taste and cooling effect in the mouth.
Even in more challenging formulations, when the active compound delivers a strong, unpleasant flavour or is required at a higher dose, functional excipients still have a role to play.
In the case of an orally disintegrating buccal dosage form, for instance, a manufacturer could complex the API with cyclodextrins to create a barrier between bitter compounds and the taste buds; but, without additional taste masking, the patient may still perceive the drug to be bland or unpleasant.
This is when a high-performance mannitol solution such as Roquette’s PEARLITOL 200 GT can add real value. Offering improved organoleptic perception, reduced friability and a better overall tablet consistency, excipient solutions such as this can be used alone or in combination with other strategies to ensure patients don’t need a spoonful of sugar to help their medicines go down.
Good for the industry, better for patients
The scale and complexity of the patient compliance issue can at times feel overwhelming. The good news for pharmaceutical brands, however, is that the strategies designed to encourage better medication adherence can also boost their bottom lines.
From selecting multifunctional excipients that reduce production costs to differentiating their offerings with convenient, safe and great tasting dosage forms, brands can do a lot for their businesses by putting patient needs first.
With a trusted excipient supplier by their side and a good understanding of the causes behind the crisis, pharmaceutical manufacturers can build a future in which no patient gets left behind.
References
- www.uspharmacist.com/article/medication-adherence-the-elephant-in-the-room.
- www.ncbi.nlm.nih.gov/pmc/articles/PMC6045499/.
- www.statista.com/statistics/317669/healthcare-expenditure-in-the-united-kingdom/.
- A.K. Mohiuddin, “Patient Compliance: Fact or Fiction?” Innov. Pharm. 10(1):10.24926/iip.v10i1.1621 (2019); retraction in Innov. Pharm. 11(1):10.24926/iip.v11i1.3941 (2020).
- www.pillsy.com/articles/medication-adherence-stats.
- https://ec.europa.eu/eurostat/statistics-explained/index.php?title=Medicine_use_statistics#Prescribed_medicines.
- https://apps.who.int/iris/bitstream/handle/10665/42682/9241545992.pdf?sequence=1&isAllowed=y.
- E.J. Huth and T.J. Murray, Medicine in Quotations: Views of Health and Disease Through the Ages, Second Edition (American College of Physicians, Philadelphia, PA, US, 2006).