FUNCTIONAL EXCIPIENTS – Much More Than Filler: Solving the Challenge of Patient Non-Compliance
The pharmaceutical industry currently faces one of its toughest challenges to date – the epidemic of patient non-compliance. Recent research suggests medical non-adherence accounts for half of all treatment failures in the US, with serious consequences.1 This phenomenon is the cause of at least 100,000 preventable deaths and generates unnecessary medical costs of up to $100 billion each year.2 The stakes could not be higher, yet progress to tackle the root causes of medication misuse has been frustratingly slow. In this article, we want to introduce the pharma industry’s secret weapon in the fight against non-compliance – functional excipients. Much more than just fillers that hold tablets together, these ingredients could help manufacturers do their part to turn the tide and drive improved health outcomes for patients around the world.
INNOVATIVE DOSAGE FORMS UNLOCKED
Alongside medical professionals, pharmaceutical drug manufacturers have an equally important role to play in encouraging improved medication adherence. For drug producers, this vital responsibility is usually discussed in the context of active pharmaceutical ingredient (API) efficacy and effectiveness, but excipient selection is just as fundamental a consideration for formulating patient-centric delivery forms.
Choosing the right functional excipient allows brands to create innovative products – from orally disintegrating tablets and films to effervescent and modified-release tablets – designed to meet both patients’ medical needs and personal preferences. Ultimately, high-quality excipients make convenient, tailored, and effective dosing methods possible, unlocking new horizons in drug delivery.
Armed with these solutions, pharma manufacturers can reduce medical waste, boost their commercial bottom lines and – most importantly – help patients feel the full benefit of their medications. By taking a closer look at some of the most exciting patient-centric dosage forms available today, it becomes clear just how important functional excipients are for encouraging patient compliance.
DEVELOPING ORALLY DISPERSIBLE DRUGS
In any solid dosage form, swallowability, ease of administration, and taste are critical considerations. These factors are imperative for all patient groups, but doubly so for geriatric or pediatric populations, who typically struggle to swallow traditional medications. To address the issues of drug accessibility for patients suffering from dysphagia (difficulty swallowing), formulators have developed a range of disintegrating dosage forms: orally disintegrating tablets (ODTs), orally dispersible mini tablets (ODMTs), and orally disintegrating films (ODFs). Dissolving rapidly when placed on the tongue, these delivery methods simplify the process of taking medication, making it safer, easier, and more convenient for the patient. Because they disintegrate quickly in the oral cavity, taste and overall sensory experience are extremely important. This is where high-quality functional excipients can really add value.
When selecting an excipient for use in ODTs and ODFs, manufacturers must pay close attention to processability, resultant mechanical strength, dispersibility, and palatability. Beyond just checking these features off a list however, balance is a crucial factor in dispersible formulations. This is particularly true when considering mechanical strength and rapid disintegration. While it is important the chosen excipient delivers good strengthening and binding capabilities, this should not hinder the rapid disintegration of the tablet or film. With such a delicate balance to achieve here, multifunctional excipients rapidly become a necessity. Solutions that combine ideal texture properties, with a pleasant flavor and ease of handling allow manufacturers to concentrate on ensuring their ODTs and ODFs can live up to their primary functional advantage – dispersibility.
Based on extensive testing, formulation scientists at Roquette developed PEARLITOL® Flash, a mannitol-starch compound, specifically designed to produce dispersible dosage forms that hit the spot for pharma producers and patients. A direct compression excipient with superior disintegrant properties, PEARLITOL® Flash offers excellent chemical inertness and consistently rapid disintegration time. Additionally, its mild taste and texture make it an ideal choice for swallowable and orally dispersible tablets.
MODIFIED RELEASE, IMPROVED RESULTS
Another significant barrier to patient compliance is pill fatigue. This phenomenon is triggered when patients feel overwhelmed by the number of drugs they must take, something that is more prevalent in geriatric populations who typically require more medications for chronic conditions.3 For most patients, compliance starts to wane beyond a certain pill count. However, some medications with a relatively short half-life require 2-4 doses daily to be effective. Traditionally, pill fatigue has been characterized as a “patient problem” by medical professionals, without taking into account just how challenging it can be to form the habits required to take multiple daily doses of several different medications.4 To help bridge the gap between efficacy and patient compliance, pharma formulators are investigating the benefits of reducing dosing frequency through controlled-release dosage forms.
Broadly categorized as extended-release formulations, these dosage forms typically feature a highly soluble BCS (Biopharmaceutical Classification System) Class I or Class III API, combined with a specialized excipient, that slowly release the required amount of drug throughout the day with just one or two doses. Apart from the obvious benefit of reducing dosing frequency, controlled-release drugs offer a host of advantages. By maintaining a more consistent level of medication in the body for example, this delivery method curbs the fluctuations that can cause under or overdosing, providing therapeutic efficacy with reduced risk of potential side effects. In recent years, producers have also begun to extend the benefits of gradual release formats beyond the realm of oral dosage forms. Multiple-day transdermal and subcutaneous depot formulations administered via transdermal microneedle patches, for instance, offer an effective, painless method for overcoming the GI barrier when delivering large molecule biologics. They are therefore gaining popularity as an alternative to traditional multi-dose oral regimens. Such features may result in improved bioavailability, safety, and effectiveness, as well as better patient compliance.
Getting down to practicalities, successful modified drug development hinges on selecting a polymeric-based excipient, capable of allowing the API to be gradually diffused from the tablet. Typically, these excipients, such as hydroxypropyl methylcellulose (HPMC), work by forming a gel-like matrix when they come into contact with the aqueous environment of the GI tract. This feature ensures the active ingredient takes longer to diffuse out of the tablet, resulting in a slower drug-release profile. In addition to the excipient type, manufacturers must also consider the proportion needed to achieve the desired rate of drug release at the absorption or target site.
To complement the effect of these slow-release ingredients, Roquette offers a broad range of directly compressible excipients, such as magnesium stearate and MICROCEL® microcrystalline cellulose, which exhibit good flow and compaction properties to help formulators develop successful controlled-release drugs. The superior stability exhibited by Roquette excipients offers another advantage – helping to ensure both reproducibility and reliability so patients experience the same outcome after each and every dose.
THE “SOFTER” SIDE OF DRUG DELIVERY
While delivery methods tend to dominate the conversation surrounding patient compliance, smart excipient solutions can go further than just addressing dosage preferences. By aligning their solutions with people’s values and ideals, as well as their physical needs, drug producers can ensure patients are not only capable of taking their medication but are actually comfortable doing so.
Take the rising demand for plant-based healthcare solutions as an example. The number of people following vegetarian and vegan diets, or simply seeking to consume fewer animal-derived products, has skyrocketed in recent years.5 As such, the widely popular softgel capsule format faces a serious issue. Due to its multifaceted functional properties and natural positioning, gelatin has historically been the excipient of choice for these applications. But with its origins as a byproduct of the meat industry, this well-known ingredient is unsuitable for veggie or vegan-friendly drug development.
Again, innovative excipients can circumvent this problem by providing brands with new opportunities to create pharma and nutraceutical products powered by plant-based materials. First-of-a-kind pea starch technologies, like Roquette’s LYCAGEL® plant-based softgel solution, give brands the option to develop vegetarian softgels that perform equally, if not better, than gelatin-based solutions, while still adhering to the stringent quality standards required in the highly regulated pharmaceutical and nutraceutical markets. Higher performing and more sustainable than other gelatin-alternatives, these plant-based solutions deliver transparent, shiny capsules with a neutral taste that are easy for patients to swallow – both literally and metaphorically.
IT ALL COMES BACK TO PEOPLE
In these technical discussions on polymer matrices, dispersibility, and optimal API delivery, it can be easy to forget the people at the center of the patient-compliance issue. Medical noncompliance is one of the most pressing issues facing the pharma industry today, but it is even more serious for patients who are not receiving the treatments they need, want, or deserve. Ultimately, optimal medication lies in the intersection of efficacy and effectiveness – wherein efficacy refers to the ability to cause a therapeutic effect and effectiveness relates to its value in real-world use.6 A general rule of thumb is that drugs tend to score lower on effectiveness than efficacy because clinicians prioritize short-term discomfort over long-term health benefits.7 But to achieve truly ideal drug delivery, manufacturers should strive to redress the balance and put patient experience on a par with a medication’s baseline efficacy.
As the range of excipients available to pharma brands increases, so do the opportunities to tackle this challenge with smart drug delivery. Game-changing APIs are undoubtedly important for improving user acceptance, but innovative excipients also deserve a place in the patient compliance conversation. A trusted excipient supplier therefore has an extremely important role to play in helping pharmaceutical manufacturers solve their formulation and delivery challenges. Much like the process of combining the right API, excipient, filler, or binder – ingredients suppliers, pharma producers, clinicians, and patients can overcome these challenges by combining forces and working together to build a healthier future for all.
- Elephant in the Room, US Pharm. 2018;43(1)30-34, https://www.uspharmacist.com/article/medication-adherence-the-elephant-in-the-room.
- Kleinsinger F. The Unmet Challenge of Medication Nonadherence. Perm J. 2018;22:18-033. doi: 10.7812/TPP/18-033. PMID: 30005722; PMCID: PMC6045499.
- Keppel Health Review, Pill fatigue, 25 February 2022, https://www.keppelhealthreview.com/winter2022/pillfatigue#:~:text=Pill_fatigue_is_when_a,they_have_to_take_them.
- Ibid, Kleinsinger F.
- Food Revolution Network, Why the Global Rise in Vegan and Plant-Based Eating is No Fad (30x Increase in US Vegans + Other Astounding Vegan Stats), 6 April 2022, https://foodrevolution.org/blog/vegan-statistics-global/.
- Shalini S. Lynch, MSD Manual, Drug Efficacy and Safety, last reviewed May 2022, https://www.msdmanuals.com/en-gb/professional/clinical-pharmacology/concepts-in-pharmacotherapy/drug-efficacy-and-safety.
- Ibid, MSD Manual.
Dr. Carin Siow is a Senior Pharmaceutical Application Scientist at the Roquette Applications Lab. She earned her Bachelor’s degree in Pharmacy and her PhD in Pharmaceutical Technology from National University of Singapore. As a registered pharmacist, she is passionate about leveraging the advantages of excipients to improve the design of dosage forms for patients. Her current role involves working on application studies and developing technical materials to broaden the formulation and processing understanding of the Roquette excipient portfolio.
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