From Complex APIs to Patient-Centricity: The Power of Oral Dosage Innovation

The oral dosage market is being shaped by a variety of innovations aimed at improving bioavailability, enhancing patient-centricity, and supporting complex molecules with sophisticated formulation solutions.

Delivering pharmaceutical products orally is still the preferred route of administration with the majority of approved, commercially available products formulated as oral doses (1). Thanks to the popularity of the dosage form, demand for oral solid drugs is continuing to rise and market research anticipates that there will be further innovations in the field to help overcome the challenges associated with the rising complexity of APIs (2).

“The oral dosage formulation market continues to grow, with oral solid dose (OSD) formulations remaining the preferred ‘gold standard’ due to cost effectiveness, stability, and ease of patient use, allowing broader access across patient populations,” remarks Rebecca Jansen, Associate Vice President — Manufacturing, Technical Services, and PDS, Bora Pharmaceuticals. “The market growth is driven by the aging patient population and the introduction of new drugs, such as GLP-1s [glucagon-like peptide-1s].”

A Dynamic Area of Innovation

“Oral dosage forms may seem like a mature field, but they are one of the most dynamic areas of pharmaceutical innovation,” asserts Brent Moody, Director, Scientific Advisory Services, Catalent.

For Dr. Srinivasan Shanmugam, Executive Director of Pharmaceutical Sciences, Adare Pharma Solutions, rapid innovation is being seen on the formulation side, “driven by three major forces: improving bioavailability; enhancing patient centricity; and developing technologies to support complex dosage forms with structurally sophisticated formulations,” he notes.

While many trends within the field of oral dosage forms have significantly impacted how medicines are developed and delivered, a key trend for Moody has been the widespread adoption of modified-release technologies. “Systems such as matrix tablets or multi-particulate formulations have enabled the design of formulations that deliver controlled, consistent therapeutic levels over extended periods,” he says. “This [innovation] has had a real impact on patient adherence and outcomes, especially in chronic disease management.”

Additionally, momentum has been growing around technologies that can aid with formulating products that were once considered difficult or even impossible to formulate, Shanmugam continues. “One area poised to reshape oral dosage formulation is 3D screen printing. Unlike traditional 3D printing methods, which often lack scalability and involve heat-based processes that can degrade APIs, 3D screen printing uses an additive manufacturing process that builds tablets layer by layer,” he says.

“This approach enables the creation of innovative dosage forms that offer unprecedented therapeutic flexibility,” Shanmugam adds. “For example, with 3D screen printing you can create a treatment that combines immediate, delayed, and extended-release mechanisms in a single tablet. The technology can also be sued to create complex multi-compartment structures that are extremely difficult to achieve with conventional technologies. It also allows for the incorporation of multiple APIs with distinct pharmacokinetic profiles into a single dosage form.”

Another major area of consideration for the OSD market has been patient-centricity, Moody continues. “The industry has moved far beyond the ‘one-size-fits-all’ mindset,” he says. “There has been a substantial increase in the availability of dosage forms tailored for specific populations, such as orodispersible tablets (ODTs) for pediatric and geriatric patients, multi-particulate formulations, and capsules that are easier to swallow or compatible with specific diets and cultural needs.”

This increased emphasis on patient-centricity is much needed, especially for pediatric and geriatric populations, confirms Shanmugam. “Patient-centric approaches often incorporate taste masking and modified-release technologies in easy-to-swallow formats to improve patient experience, convenience, and adherence, with the use of multiparticulates, ODTs, and flexible dosing formats like chewables and sprinkles,” he adds.

A key focus for industry, however, has been on overcoming poor solubility and bioavailability, “which affect a large proportion of today’s small-molecule drugs. We have seen self-emulsifying drug delivery systems (SEDDS), amorphous solid dispersions, and other technologies become mainstream,” Moody remarks.

“As development pipelines become increasingly saturated with more complex and poorly soluble molecules, formulation approaches are shifting,” concurs Jansen. “Solubility-enhancing methods such as solid amorphous dispersions using spray drying technology and hot melt extrusion, especially when paired with lipids, are being utilized to further optimize solubility.”

Enabling Oral Absorption

“The continued advancement in biology, along with a deeper understanding of disease mechanisms and the cell biology of target proteins, has significantly increased the complexity of molecular properties, and consequently, the challenges associated with oral absorption. Factors such as molecular size, shape, and solubility are major contributors to this complexity. In many cases, these challenges necessitate the use of enabling technologies,” explains David Vodak, Ph.D., Chief Scientific Officer, Bend Bioscience.

By way of example, Vodak points to the novel class of molecules proteolysis targeting chimeras (PROTACs), which have expanded the potential druggable targets but are often poorly soluble/permeable, leading to low bioavailability. “Molecules with low permeability, in particular, present a challenge for formulators, requiring innovative approaches to enhance the bioavailability of oral drug products. This [challenge] has led to the development of strategies such as the use of permeation enhancers and complex formulations designed to deliver the active ingredients more efficiently,” he says.

“Poor solubility and/or low permeability are still the biggest hurdles we face as formulators,” confirms Moody. “The chemical space we’re exploring for new drugs, whether traditional small molecules or complex modalities like heterobifunctional degraders, is producing compounds that are often highly potent but difficult to formulate for adequate bioavailability and consistent patient outcomes. As a result, formulation strategies are evolving quickly.”

As mentioned earlier, enabling technologies, such as lipid-based formulations that use the body’s natural lipid processing pathways to improve solubilization and absorption, are becoming more widely used for oral delivery, Moody notes. “Amorphous solid dispersions (ASDs) remain a go-to strategy for many poorly soluble drugs. Advances in polymer science and processing techniques, like spray drying, are helping us better stabilize these systems, achieve higher drug loads, and optimize drug release,” he states. 

Tools, such as spray drying and hot-melt extrusion (HME), that allow drugs to be molecularly dispersed in polymer matrices are important in improving solubility and bioavailability, Shanmugam points out. Additionally, nanonization and micronization are being employed by formulators to increase surface area and improve dissolution rates with greater control than other approaches, he adds.

Predictive modelling and in-silico tools, such as physiologically based pharmacokinetic modeling (PBPK), are being used to guide early formulation as well, highlights Moody. “[These tools help] teams make more informed decisions and reduces the reliance on time-consuming empirical screening,” he says.

“Additionally, new technology approaches, like smart pills and dosage formats with targeted release profiles and extended residence times, [have been highlighted at industry events] as examples of the innovative solutions that are shaping the future of oral drug delivery,” emphasizes Vodak.

“Combining technologies is increasingly common, as no single approach fits all APIs,” specifies Shanmugam. “The focus is on building flexibility into the formulation strategy to match the characteristics of each molecule.”

Patient-Centricity is a Central Focus

Oral dosage formulation is being shaped by patient centricity, particularly in consideration of particular patient populations, such as geriatric and pediatric patients, who can experience greater difficulties with medication adherence, Shanmugam stresses. “Innovations today are focused on improving not just efficacy, but the entire patient experience,” he says.

“Patient-centricity has indeed become a central focus in drug development, and recent innovations in oral dosage formulation are increasingly aimed at improving patient experience, adherence, and outcomes,” confirms Vodak. “One major area of innovation is the development of innovative dosage forms that address patient needs in terms of ease of administration, taste masking, and convenience.

Providing an example, Vodak points to ODTs, which have become popular thanks to their rapid buccal dissolution rate thus making administration to patients with swallowing difficulties easier. “In parallel, advancements in taste-masking technologies are addressing one of the most common barriers to patient compliance, unpleasant-tasting medications. By using novel excipients, coatings, or microencapsulation techniques, formulators can improve the palatability of drugs, making them more acceptable, especially for children or patients on long-term therapy,” he states.

“Another popular patient-centric option is multi-particulate formulations delivered in flexible stick packs. These consist of tiny, coated pellets, granules, or even liquid-filled softgels, which can be sprinkled onto soft food, suspended in liquids, or in some cases, taken directly,” Moody remarks. “This approach offers flexible dosing and ease of swallowing, particularly benefiting children or elderly patients who struggle with whole tablets or capsules. Plus, multi-particulates can be engineered for controlled or targeted release, further enhancing therapeutic outcomes.”

Reducing dosing frequency through extended-release formulations and multilayer tablets can also improve patient convenience and comfort, Vodak continues. “By releasing the drug over an extended period, these formulations reduce the need for multiple doses per day, improving patient adherence and simplifying treatment regimens,” he says. “These formulations are especially beneficial for chronic conditions where long-term medication adherence is essential for effectiveness.”

Innovations in smart pills and digital health technologies are not only enhancing dosage form functionality but are also providing greater insights into medication adherence, Vodak adds. “Smart pills, for instance, can incorporate sensors that transmit data to a patient’s smartphone or healthcare provider, helping to ensure that the patient is taking the medication as prescribed. This is particularly valuable in managing chronic conditions where long-term medication adherence is critical. Additionally, digital platforms linked with medication regimens are providing better engagement and educational tools for patients, helping them understand their treatment and stay on track,” he says.

Additionally, tailoring formulations by using genetic or biomarker data is gaining momentum and allowing for more precise and effective dosing, Vodak specifies. “Personalized dosage forms, such as capsules that can be customized in terms of dose or release profile, are becoming increasingly common and are especially beneficial for patients who require adjustments to their therapy over time,” he confirms.

“Lastly, there has been an increasing focus on sustainability in oral dosage forms,” Vodak emphasizes. “With patients becoming more environmentally conscious, formulators are exploring ways to reduce the environmental footprint of packaging and manufacturing. This includes the use of biodegradable packaging, reduced material waste, and the move towards more sustainable production methods.”

Meeting Evolving Needs

Various innovations are helping to improve oral solid dosage forms, making them more patient-centric, helping to overcome challenges with solubility and bioavailability, and becoming more sophisticated to deal with increasingly complex APIs. “These advancements are focused not only on enhancing the ease of use and patient adherence but also on personalizing treatment and integrating technology to offer more tailored, effective, and convenient options,” summarizes Vodak. “As patient expectations continue to evolve, these innovations will likely play a key role in improving patient outcomes and satisfaction.”

While the oral dosage form market remains robust, emphasis from industry has shifted towards the development of new chemical entity-based products, the success of which will be “driven by a combination of factors, including quality, speed to market, and the integration of cutting-edge enabling technologies,” Vodak concludes. “These elements are critical in ensuring the successful development and commercialization of novel oral dosage forms that meet the evolving needs of patients and the industry.”

References

1. Kotsybar, J.; Hakeem, S.; Zhang, L.; Jiang, W. Global Harmonization of Immediate-Release Solid Oral Drug Product Bioequivalence Recommendations and the Impact on Generic Drug Development. Clin. Transl. Sci. 2023, 16 (12), 2756–2764.

2. Roots Analysis. Oral Solid Dosage Manufacturing Market — Distribution by Type of Finished Dosage Form, Type of Packaging, Scale of Operation, Company Size, Therapeutic Area, and Key Geographical Regions: Industry Trends and Global Forecasts, Till 2035. Market Research Report, September 2023.

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