Uncover the 4 toughest oral liquid formulation challenges — and how to solve them
Medicines are designed to support health, but if patients are reluctant to take them due to unpleasant dosing experiences, they may miss out on the benefits, and overall quality of life can suffer. One common hurdle to medicine adherence is difficulty swallowing traditional tablets, especially for certain patient groups like babies, children, and older adults, or those suffering from pill fatigue. For these patients, liquid oral dosage forms are often the preferred delivery format.
Oral liquid formulations are available in two main formats: suspensions and solutions. Suspensions contain insoluble drug particles dispersed in a liquid. They are available in a ready-to-use liquid dosage form or dry powder formats that can be reconstituted by the patient, caregiver, or pharmacist. Solutions are homogeneous mixtures in which a drug is completely dissolved in a solvent, ensuring uniform drug distribution, consistent dosing, and rapid absorption.
While these oral liquid formulations can support better adherence to therapies and, ultimately, treatment outcomes, they are not without their own set of challenges including stability issues, poor mouthfeel, and unpleasant taste. However, with the right excipient solutions drug developers can turn these drawbacks into patient-centric liquid oral dosage forms that encourage adherence and offer additional benefits like sustained drug release. Keep reading to explore four key challenges to be aware of if you want to develop more patient-friendly options — and how to overcome the challenges with advanced excipient ingredients.
Challenge 1: Maintaining suspension stability in complex oral liquid formulations
Even the most time-tested pharmaceutical ingredients can falter in oral liquid formulations if they’re not paired with the right viscosity modifiers and suspending agents. The result? Destabilized formulations that don’t perform as intended. When it comes to suspensions, all ingredients must be uniformly dispersed to be fully functional and to allow accurate dosing. Achieving this outcome depends on having a stable suspension formulation. However, maintaining consistency can be challenging — especially in formulations with low pH levels, high salt content, or increased ionic strength (from dissolved salts) which can lead to ingredient separation over time. As such, suspensions that were stable during development could become unstable during storage.
The solution? Effective suspending agents work by forming a three-dimensional gel-like network throughout the liquid medium. This network physically traps drug particles, preventing them from settling while still allowing the formulation to flow when needed. Let’s look at colloidal microcrystalline cellulose (cMCC), such as Avicel® RC-591 and Avicel® CL-611, as an example. These excipients form a robust thixotropic gel structure when activated in water — maintaining the formulation network during storage but allowing it to flow easily under shear stress (like pouring from a bottle). This performance is the reason why our Avicel® CL-611 and Avicel® RC-591 excipients are used in popular children’s pain-relief liquid medicines.
Other excipients that can help stabilize the suspended particles in an oral liquid formulation are cellulose ethers, such as hydroxypropyl methylcellulose (HPMC). HPMC at different viscosity grades — like those available in our METHOCEL™ portfolio — allow formulators to fine-tune rheological properties (the flow and behavior of a formulation under applied stresses or force), supporting stability and improved suspension performance. When it comes to high salt formulations, some common stabilizers can stop working properly. Here, drug developers can benefit from using seaweed-derived polymers like alginates to support stability. Seaweed-derived polymers rely on ions (like those from salt) to form gels, meaning their structure strengthens in salty environments. As a result, they can help keep the product consistent and well-structured even at high salt levels while also contributing to a smooth mouthfeel.
Having the right combination of excipients maintains suspension stability to ensure that every dose delivers exactly what the prescription calls for, from the first day of treatment to the last, giving patients and caregivers confidence in consistent therapeutic outcomes.
Challenge 2: Balancing stability with viscosity and pourability
Getting the viscosity right — thick enough when still, thin enough when poured — is essential for an effective suspension. At rest, more viscosity is needed to help stabilize the active pharmaceutical ingredient (API) within the suspension to prevent sedimentation and aggregation of particles. However, when administered, a suspension must become less viscous so it can be poured. Achieving this balance is a delicate act — too thin, and particles settle rapidly; too thick, and the texture is unpleasant.
The solution? Excipients like cMCC exhibit thixotropic behavior — a decrease in viscosity under stress followed by a gradual recovery when the stress is removed. This property allows suspensions to remain stable on the shelf for extended periods while still pouring easily when needed. After pouring, the structure progressively rebuilds, helping maintain uniform particle distribution between doses and supporting both accurate dosing and ease of administration.
Challenge 3: Achieving sustained drug release
For patients managing chronic conditions, such as hypertension or diabetes, therapeutics with sustained drug release properties can be beneficial. Sustained release medicines provide predictable drug concentration in the bloodstream over a long period of time, which is essential for efficacy and means patients don’t need to take their medications so frequently. However, achieving sustained release in oral liquid formulations presents unique challenges compared to solid dosage forms, and therefore, requires specific excipients.
The solution? Modified release coatings are one effective way to achieve sustained release in oral liquid formats. For instance, ethylcellulose excipients, like our ETHOCEL™ brand, can be used to coat multiparticulate drug cores, which are then dispersed throughout the liquid suspension to provide controlled drug release over an extended period of time. This means that while the patient swallows a liquid medicine, the sustained-release profile is delivered by the coated particles rather than by the liquid itself.
Challenge 4: Creating a pleasant sensory experience
Even the most stable, well-formulated suspension fails if patients refuse to take it due to an unpleasant sensory experience, like poor palatability or mouthfeel. This is particularly critical in pediatric populations where taste and texture issues can make the administration of medicine a daily battle. Bitterness is a key challenge here. In fact, a model used to predict bitterness based on the chemical structure of an API has revealed that around two thirds of clinical and experimental drugs are likely to elicit some degree of bitterness.i Overcoming this sensory challenge is critical to the acceptance and therapeutic benefit of an oral liquid formulation.
The solution? Using multiple excipients can help improve sensory properties — from pleasant texture to enhanced taste. cMCC, for instance, is known for creating a smooth texture that patients find pleasant and easier to swallow. Whereas rheology modifiers like cellulose ethers allow control over viscosity and flow properties. This enables formulators to achieve the ideal consistency — smooth enough to pour and provides swallow comfortably. What’s more, seaweed-derived polymers including alginates and carrageenan can also contribute towards distinctive textural properties and exceptionally smooth mouthfeel. Sweeteners, like dextrose and glucose, can improve the palatability of liquids containing off-tasting APIs; often a necessity when formulating for pediatric populations. And as for taste masking, modified release coatings can encapsulate bitter drug particles within suspended multiparticulates, preventing direct contact with taste receptors while maintaining suspension stability. Cyclodextrins, such as Roquette’s KLEPTOSE® range of beta‑cyclodextrins, provide an additional taste‑masking solution by forming inclusion complexes with bitter APIs, effectively reducing their interaction with taste receptors. Available in both pharmaceutical and food grades, KLEPTOSE® beta‑cyclodextrins can be used in liquid and tablet formulations to improve palatability while maintaining API performance.
Ready to create oral liquid dosage forms that deliver on performance and patient experience?
Roquette has the expertise and portfolio to help drug developers overcome common complex formulation challenges — opening the door to more patient-centric oral liquid dosage forms.
Want to know more? Download our scientific guide to see how cMCC excipients can help you overcome common challenges in your oral liquid suspensions like accurate dosing and unpleasant texture: Colloidal Avicel® for Suspensions Applications
1 Dagan-Wiener, A., Nissim, I., Ben Abu, N. et al. Bitter or not? BitterPredict, a tool for predicting taste from chemical structure. Sci Rep7, 12074 (2017). doi.org/10.1038/s41598-017-12359-7
