Oral liquid dosage forms are essential in the pharmaceutical industry, catering to the needs of patients who have difficulty swallowing solid tablets, such as children and the elderly. Liquid formulations also allow for more precise dosing, particularly beneficial in therapeutic areas such as oncology. These formulations enable healthcare providers to more easily adjust dosages according to a patient’s specific needs, enhancing treatment efficacy and adherence.

Catherine Lloyd is Senior Process Optimisation Scientist at PCI Pharma Services. “Oral liquid dosages are best suited for therapeutic areas where patients have difficulty swallowing, require flexible or personalised dosing, or where patient compliance is a significant concern – most notably in paediatrics, geriatrics and oncology,” says Lloyd. “For instance, in oncology, you tailor the dose based on body weight. That’s a lot easier to do with a liquid product.”

This flexibility is one of the factors driving innovation, ensuring oral liquids remain user-friendly and foster patient compliance. This focus on patient-centric solutions is vital as the industry strives to meet the evolving therapeutic needs of diverse populations. However, the pharma landscape is currently witnessing a rising prevalence of poorly soluble drug molecules. According to multiple scientific publications, about 40% of drugs with market approval and 70-90% of molecules in the discovery pipeline exhibit poor solubility, directly impacting their bioavailability and therapeutic effectiveness. As a result, there is a growing demand for oral liquid formulations that can effectively deliver these poorly soluble drugs, thereby driving evolution of the market.

Beyond the solubility challenge, oral liquid dosage forms present a range of unique considerations in their development and manufacturing, requiring careful attention to taste, stability, packaging, and scalability, all while navigating changing regulations and patient needs.

The matter of taste

Taste masking is a multifaceted challenge that requires a combination of flavour science, excipient technology, patient preference analysis, and sometimes, innovative analytical tools. The goal is to make the medicine as palatable as possible to ensure patient compliance, especially for children and the elderly, who are particularly sensitive to unpleasant flavours. One of the main strategies is the use of flavours to either mask or complement the taste of the active pharmaceutical ingredient (API).

Louise Carpenter is Head of Pharmaceutical Development at PCI Pharma Services. She explains: “There are some nasty tasting drugs you are never going to be able to mask and you are better off complementing. For bitter drugs, we might bring my favourite flavour in – cherry – a really good flavour to mask or complement with.”

Of course, flavour choice is heavily influenced by target population and regional preferences. For example, Carpenter says that strawberry is the most popular choice for children, but notes that the strawberry flavour preferred in the UK is different to the one preferred by the German market. Working with flavour houses and understanding local preferences is essential, she says.

Another part of the challenge is that it’s hard to taste-mask products when you can’t taste them yourself. When it comes to potentially toxic oncology drugs, technological approaches to taste assessment are used. For example, the ‘E-tongue’ is an electronic device that mimics human taste perception when human testing is not possible. Carpenter notes that PCI Pharma also collaborates with universities on projects such as taste profiling.

As well as the API, excipients can also play a role in taste. Cyclodextrins, for example, can help mask certain tastes, though they are “fiddly to work with,” according to Carpenter. Sweeteners such as sucralose or sorbitol may be added, but these come with their own challenges, including potential intolerance and regulatory scrutiny. Other advanced methods include coating the API to prevent its taste from being immediately detected and working with manufacturers to explore encapsulation or other physical modifications.

Solubility and bioavailability issues

Poor solubility can limit the effectiveness of a drug, as it may not dissolve sufficiently in the gastrointestinal tract to be absorbed into the bloodstream. The industry is responding with innovative technologies, with many companies forming partnerships with technology providers specialising in solubility enhancement. Nanoparticle technology and spray drying are among the advanced techniques being used to improve the solubility of challenging APIs. Carpenter explains: “We’ve established strategic partnerships with solubility enhancement experts with a range of capabilities to enhance our service offering to clients. We act as the single point of contact, finding the right solution for our clients’ product – a product-first, platform-agnostic approach, rather than applying a single solution to all products.”

Bioavailability – the proportion of a drug that enters the circulation and can have an active effect – is closely linked to solubility. Innovative formulation strategies to ensure that enough of the drug is absorbed include lipid-based formulations that coat the API; self-emulsifying drug delivery systems which dissolves the drug into an oil; and nanosuspensions, creating a smaller API which suspends easier with less excipients and solubilises more quickly in the intestine. Advanced formulation techniques are particularly important for high-cost, potent drugs such as those used for oncology or rare diseases, where maximising absorption is critical for both efficacy and cost-effectiveness.

Maintaining product integrity

The stability and correct containment of oral liquid dosage forms involve a delicate balance of formulation science, packaging technology and regulatory compliance. The goal is to maintain product integrity and safety throughout its shelf life, while also meeting the practical needs of patients and healthcare providers.

Oral liquids are susceptible to microbial growth, requiring careful selection and justification of preservatives. Regulatory scrutiny is also increasing around extractables and leachables – chemicals that can migrate from packaging materials (like plastics) into the drug product over time. The choice of container, such as plastic versus glass, and the need for nitrogen overlay or oxygen headspace management, are also important for maintaining product stability. This can mean more stringent testing and careful selection of packaging materials to ensure that nothing harmful leaches into the product during its shelf life.

Speaking on draft regulations mandating that packaging design and compatibility be addressed early in development, Lloyd says: “Liquid in some products can be in that bottle for 48 months plus, so a lot more testing will be needed on the horizon.”

For oral liquid containment, the choice between single-use and multi-dose containers has significant implications for both stability and patient safety. Single-use containers reduce the risk of contamination and eliminate the need for preservatives but may increase environmental waste and logistical complexity. Multi-dose containers, however, require robust preservative systems to minimise contamination risk with repeated use.

Scalability and manufacturing flexibility

The market is moving towards smaller, more personalised batches, especially for niche indications, so manufacturing systems need to be flexible enough to handle varying batch sizes, rapid changeovers and potentially more complex formulations. However, with large-scale products still dominating capacity, freeing up manufacturing lines for new formulations can be a challenge.

Manufacturing flexibility also extends to implementing new technologies, such as advanced solubility enhancement or novel packaging solutions, without disrupting existing operations. This may involve investing in modular equipment, multipurpose lines, or new facilities designed for rapid reconfiguration.

Ultimately, the future of oral liquid dosage forms will be shaped by the ability to balance innovation with practicality, ensuring that medicines remain effective, safe, and accessible.

To learn more about high-potency APIs and their role within the wider industry trend towards targeted modalities, please download the whitepaper below.