While the broader public may be familiar with the breath-freshening strips found at convenience stores, many are unaware that similar “thin films” also have an application in the pharmaceutical market. Referred to as oral thin films (OTFs), they have proven very useful for patients who have trouble swallowing, because drugs can be delivered without the need to chew or swallow. Such patients include children, those experiencing nausea, and the growing elderly community1 – altogether 37 percent of the population.2 While the industry is still in the process of optimizing OTF development with the right methods and expertise, the need for this system is apparent.
What are oral thin films?
OTFs are polymeric films designed to deliver therapeutic moieties into the oral cavity or the gastrointestinal (GI) tract, where they are absorbed and routed to the circulatory system directly. As such, OTFs can rapidly deliver hydrophilic as well as hydrophobic active compounds.
There are two main types of OTFs – oromucosal and orodispersible. The former sticks to various parts of the oral cavity and slowly releases the drug into the patient’s systemic circulation. Drugs from these films enter the circulatory system directly, and thus, bypass first-pass metabolism. In contrast, the latter (orodispersible) breaks down immediately upon contact with saliva.
Within orodispersible films, there are two subtypes: orally disintegrating, which disintegrate in the mouth, then dissolve and are absorbed in the GI tract (poorly water-soluble drugs); and orally dissolving, which disintegrate and dissolve simultaneously in the mouth (water soluble drugs).
OTFs can be characterized by organoleptic traits (e.g. taste and color) that appeal to the senses but do not affect performance, mechanical traits important for manufacturing, handling, and transportation of the drug (e.g. tear resistance), and performance traits (e.g. disintegration/dissolution rate) which explain how the thin film will actually release the drug inside the body for therapeutic effect.
Advantages for delivering drugs
OTFs are emerging as a promising drug delivery system due to their patient-friendly characteristics, precise and flexible dosing, and simple manufacturing process.
This drug delivery system is an attractive option for patients because they don’t need to chew, swallow or use water to ingest the drug. The thin film covers a relatively large surface area, which allows for faster disintegration and dissolution. They can also be given a likable flavor and color for easy administration in children.
Because the films can be manipulated for precision dosing, this is useful for several cases, including children who often need smaller doses, adults who need partial doses, and drugs in development where the production doesn’t include large doses.
Compared to tablets and capsules, manufacturing OTFs is much simpler and faster because of fewer process steps. This can be attributed to the fact that films can be developed with powderless and even aqueous-based processes that do not use solvents, and ultimately, allow for continuous processing.
Furthermore, OTFs are a great option for patent-expiring drugs (product line extensions), as the approval of a novel oral film application would allow these drugs to claim market exclusivity for another three years.
New applications for this drug delivery system continue to arise. It was previously thought that OTFs could not carry water-insoluble drugs. However, recent research has shown that BCS Class II/IV drugs (classified as having low solubility by the Biopharmaceutical Classification System) can actually be incorporated into orally disintegrating films.3
Improvements needed in OTF development
Although OTFs offer many advantages for drug delivery, they are still a novelty that requires more research and optimization in order to deliver a wider range of drugs, particularly water-insoluble ones. Unlike tablets and capsules, OTFs often do not carry additional solubilizers – they rely mainly on polymers to increase a drug’s solubility. So, developers must explore innovative particle engineering techniques to improve delivery of water-insoluble drugs via thin films.
OTFs also come with certain limitations in the areas of packaging and dosing. For example, the larger and thinner surface that provides several advantages, is also more sensitive to humidity and temperature, requiring special packaging. In the same vein, while OTFs are ideal for small drug loads, they don’t work well for drugs that need a large dose.
The development process for OTFs has come a long way. But testing and characterization aspects still need more improvement. The US Pharmacopeia does not currently have methods or monographs designated for this purpose. Further, because methods and endpoints are not clearly defined, there can be inaccuracy when assessing OTF effectiveness. It’s difficult for researchers to even draw guidance from other USP-prescribed tests for tablets and capsules because there are too many differences between the two systems.
Because there is not much guidance on how to develop and test OTFs, the companies in this business must have experience in working with novel drug delivery systems, developing formulations, and navigating the regulatory processes that affect OTF development. The best practice in the industry is to take a customized approach that selects for OTF components based on their chemical properties. Having this type of expertise would likely yield more efficient OTFs with a higher chance of success in the clinic.
1. United Nations. (n.d.). Ageing. Retrieved from: https://www.un.org/en/sections/issues-depth/ageing/
2. Schiele, J.T., Quinzler, R., Klimm, H. et al. (2013) Difficulties swallowing solid oral dosage forms in a general practice population: prevalence, causes, and relationship to dosage forms. Eur J Clin Pharmacol. 69: 937–948. DOI: https://doi.org/10.1007/s00228-012-1417-0
3. Krull, S. M., Ma, Z., Li, M., Davé, R. N., & Bilgili, E. (2015) Preparation and characterization of fast dissolving pullulan films containing BCS class II drug nanoparticles for bioavailability enhancement. Drug Dev. Ind. Pharm. 42(7):1073–1085. DOI: 10.3109/03639045.2015.1107094
Dr Shanmugam has more than 15 years of experience with design and development of conventional, NDDS/alternate advanced/modified drug delivery systems, and platform technologies. He has successfully designed, developed, and implemented various platform technologies to enhance oral bioavailability of highly hydrophilic as well as poorly soluble/bioavailable highly lipophilic drugs. He has managed many global product development collaborations with big pharma. Additionally, Dr Shanmugam has published numerous research articles in prestigious pharmaceutical sciences journals and presented more than 20 of his works in various symposiums/conferences globally. He is also a reviewer and editorial member of various journals.