The move towards patient centric dosing

Shawn Branning, global strategic marketing manager at IFF offers a look at oral thin films and how they’re becoming a growing solution for patient-centric dosing. 

Children and geriatric populations can present unique challenges when it comes to utilising traditional oral drug delivery formats, such as tablets and capsules. These include choking risks, the possibility of dosing inaccuracies due to spitting out the drug and limited dosage size options. In addition, there’s portions of the population who have difficulty with swallowing medications or simply don’t have access to clean water, necessary for dosing. 

While cutting and grinding tablets may seem like a viable option for overcoming swallowing challenges, doing so can often result in an altered release profile for the drug and poor taste. It can also cause unintended exposure to the active pharmaceutical ingredient (API).

Oral thin films (OTF) – a novel drug delivery system consisting of quick-dissolving films placed in the patient’s mouth – may be the answer. They provide a patient-centric alternative for populations that have difficulty swallowing, as well as for patients that may be unconscious, uncooperative or in urgent need of medication. The adaptable design of OTFs allows them to deliver synthetic and natural APIs, as well as nutrients, in an easily consumed format that’s convenient and appealing.

Gaining popularity in the pharmaceutical space

Currently, OTFs can be used to treat myriad conditions for patients, from allergies to migraines and pain relief to preventative therapies and dietary supplements. The flexibility of the dosage form means there’s plenty of room for future uses like vaccines and biologics. In fact, according to Roots Analysis Market Research, the overall oral thin film drug delivery market is expected to grow to approximately $2.1 billion by 2025.

Understanding the structure and formulation of OTFs is critical for manufacturers looking to break into the market. While the OTF dosage form is highly adaptable, there are challenges to creating an effective and appealing end-product, including stability, organoleptic properties like taste, physical strength, drug uniformity and more.

It’s vital to choose the right excipient package to formulate effective but pleasant dosages to ensure patient compliance.

Flexible dosing for all patients

There’s no one size-fits-all approach when it comes to patient needs. OTFs provide options for targeted treatment, ranging from single layer to multi-layer films capable of a variety of structures for specific API and treatment needs. Each type of OTF is designed specifically to solve various patient challenges.

In general, we can break down OTFs into three categories based on drug release timing:

1. Fast Dissolving Orodispersible: Placed directly on the patient’s tongue, these OTFs have a high rate of release, dissolving in one to 30 seconds. Given the speedy dissolution and ease of placement, this format is considered excellent for children and the elderly, as well as those in need of fast medication delivery.
2. Buccal Films: The buccal film’s placement is inside of a patient’s mouth on the cheek. With this type of OTF, patients experience a fast onset of action with a moderate to slow dissolution of one to 30 minutes. Benefits of the buccal film include no first-pass effect and a delayed/reduced Cmax.
3. Sublingual Films: Considered the most prolonged release of the OTF formats, sublingual films take 30 minutes or longer to fully dissolve. The under-the-tongue placement enables a fast onset of action, while also preventing a first-pass effect.

With such specific release profiles, it’s critical for formulators to understand the composition of oral thin films to achieve positive outcomes. Each ingredient plays a vital role in delivering the drug to patients, while also contributing to a positive experience overall.

Understanding key players in oral thin film composition

Like other traditional oral drugs, the efficacy of OTFs lies in the careful selection and composition of ingredients. Typical OTF components consist of the API, hydrophilic film forming polymer, plasticizer, stabilizer, pH modifier, buffer, colour, flavour, fillers and taste masking agents. Of those ingredients, the polymer is the backbone for the formation and structure of the physical film.

Two of the most common polymers used in OTFs are polyethylene oxide (PEO) and hydroxypropyl methyl cellulose (HPMC). Our POLYOX technology is an example of a film forming PEO polymer. It forms flexible films that are resistant to tearing, have a fast dissolution rate, a pleasant mouthfeel and no sticky feeling or highly viscous gel formation. Additionally, METHOCEL is our HPMC technology that can be used as a film former in OTFs to create flexible, transparent, flavourless, colorless, tasteless, and water-soluble thin films.

Anionic polymers are another class of materials providing unique benefits in OTFs. Sodium carboxymethyl cellulose (NaCMC) polymers provide excellent clarity in films and can be easily plasticized using materials such as glycerol and sorbitol. Alternatively, seaweed-based biopolymers, like alginates and carrageenan, are another polymer material option that deliver solubility properties, while also being a plant-based, vegan-friendly option for formulators.     

Although polymer selection is crucial to the success of the physical film structure and stability, it’s important to look at the full picture through the lens of the patient. Polymers play a role in developing the OTF’s organoleptic properties, which is why it’s important to choose the right ones for your specific formulation needs. However, sometimes there’s no avoiding additional ingredients to ensure a pleasant drug experience. The challenge here becomes optimising ingredient selection to avoid having to add too many components to the formulation.

Overcoming taste-related formulation challenges

Patient compliance is largely tied to the overall drug experience, with taste being a key organoleptic property for this drug format since they dissolve in the mouth of the patient. Understanding taste and how to appropriately mask taste in thin films can be especially challenging for formulators because the addition of taste masking agents can reduce the potential maximum drug load of the OTF. The good news is that there are several avenues for formulators to explore when it comes to improving taste in OTFs.

Taste modulation through flavouring is one of the simplest ways to make an OTF palatable. With our deep background and understanding of flavours, we’ve developed an effective approach to help select the best flavor for a formulation based on market understanding, demographic analysis, product base flavour and the type of product. However, flavours can’t always overpower the unpleasant taste of other ingredients. Various products such as receptor blocking agents, cooling agents and sweeteners can also be successful at masking tastes.

Employing taste masking technologies is also effective. One option is utilising a barrier coating to block unpleasant tastes. Reverse enteric and water insoluble polymers such as our ETHOCEL technology are efficacious barrier coatings. Other options include microencapsulation, solid dispersion, and inclusion and complexation.

Regardless of the formulation route you take for taste, the best way to ensure success is partnering with an experienced supplier.

Partnering for oral thin film formulation success

OTFs continue to evolve in the pharmaceutical space, expanding beyond over-the-counter products to a drug delivery format suitable to treat a variety of conditions. And, as personalised drug treatment becomes the norm, oral films will play an even more substantial part in drug delivery. However, OTFs are an emerging dosage form and there’s little compendial guidance for drug developers. That’s why it’s essential to have a partner that can help navigate the complexities of various quality standards and get your product to the market safely and quickly.