Taste and Appearance: Selecting the Right Excipients

Published on: 
Pharmaceutical Technology, Pharmaceutical Technology, January 2022 Issue, Volume 46, Issue 1
Pages: 26–27, 45

Dosage form and patient needs drive excipient choice.

Medication adherence is a crucial issue today, and drug manufacturers are seeking to develop drug products that meet the needs of patients with respect to ease of use and palatability. For oral formulations, taste, appearance, and smell have a direct impact on medication adherence. Choosing the right excipients to provide optimum performance is therefore an important part of the drug development process. Various factors must be considered, from the API properties to the dosage form and the characteristics of the patient population.

Multiple approaches for different dosage forms

Oral dosage forms available today include traditional and fast-disintegrating tablets; capsules; chewables and gummies; lozenges and other suckable products; effervescent, buccal, sublingual, and thin-film formulations; suspensions, syrups, sprays, gels, sachets, stickpacks, and chewing gum; among others. The large number of different formulation types creates the need for many different approaches to improving taste and appearance. For solid formulations designed to be swallowed, particularly tablets, taste-masking and appearance are generally achieved using film coatings, according to Alen Guy, technical director IMCD Pharmaceuticals.

Such coatings prevent the API from being dissolved in saliva and interacting with the taste buds in the mouth before the drug product is swallowed, adds Nasrin Mahmoudi, AD&I scientist, Pharma Solutions with IFF. She also notes that coatings can help with appearance by providing a shiny, matte, or colorful look and hiding undesirable surface properties.

Capsule formulations are a little different from tablets. “Capsules generally don’t require taste masking unless they are designed to be opened and sprinkled onto a food or poured into a drink. Appearance is important for this oral dosage form, however, and color and design are often used to distinguish different products,” he observes.

For oral dosage products in which a bitter API does come in contact with saliva and taste buds in the mouth, different sweeteners are often used depending on the dosage form, Guy says. For instance, Elizabeth Tocce, AD&I scientist, Pharma Solutions at IFF, points to the use of sweeteners, often in combination with texture modifiers, in orally dissolving tablets (ODT), chewable tablets, oral thin films, and sachet formulations that stay longer in the mouth.

“Taste modification using flavors and other additives is more complicated, though,” Guy comments. Even so, it is often needed. “In many cases, and for very bitter high-dose drugs in particular, just changing the organoleptic properties is not sufficient, and other methods to create a physical or chemical barrier around the drug particles, such as microencapsulation and complexation, are used,” Tocce explains.

The method employed largely depends on the API characteristics and the intended dosage form, agrees Krizia M. Karry, head of global technical marketing for BASF Pharma Solutions. “Poorly water-soluble APIs with adequate dissolution rates (i.e., BCS [Biopharmaceutics Classification System] II APIs) tend to be micronized and compressed into tablets. At low dosages, adding flavors or sweeteners can suffice to ensure palatability as most tablets are not meant to disintegrate in the oral cavity, but flavors will not suppress bitter tastes,” she says. At high drug loadings and for orodispersible products, Karry adds that film coating with methacrylate copolymers that are insoluble at saliva pH is the most effective technology.

If the unpleasant taste is related to grittiness or chalkiness in chewable tables, ODTs, or suspensions, a common method is to use finer grades of the APIs and excipients, according to Tocce.

Liquid prescription drugs are particularly popular in the EMEA (Europe, the Middle East and Africa) market, where there is a preference for the dosing flexibility and a perception that they offer rapid relief, according to Karry. In North America, meanwhile, liquids are mostly offered for over-the-counter cold and flu medications. In most of these liquid formulations, she observes that highly concentrated sweeteners and flavors are typically employed to mask the bitter API taste. In formulations where multiple APIs are combined including some that are bitter or where product shelf-life is of concern, however, Karry observes that insoluble polymers are used to envelop API particles and allow their suspension in the continuous liquid phase.

For liquids, other options if sweeteners aren’t sufficient, in addition to microencapsulation and complexation, include using an insoluble form of the API and adjusting the pH of the solution to lower the API solubility, according to Mahmoudi. She adds that viscosity enhancers and texture modifiers are also used. Alternatively, taste and appearance issues with liquid formulations can be overcome by containing them in soft or hard capsules.

Wide range of excipient choices

Many different types of excipients are used to improve taste and appearance. Because the most common taste challenge is the bitterness of APIs, sweeteners, both natural and artificial, are the most commonly used taste-modifying excipients. Beyond compounds such as sugar, mannitol and sucralose, actual flavoring agents (orange, mint, etc.), flavor-maskers, particularly bitter-maskers, texture modifiers (co-processed microcrystalline cellulose and guar gum), and polyols are used. Complexing agents such as cyclodextrins and ion-exchange resins are often used for improving the taste of liquid formulations and orally dissolving dosage forms, Mahmoudi states.

“Depending on the formulation, different approaches to taste and flavor modification are needed,” Guy says. In fast-dissolve forms, short intense flavor bursts are needed, while in longer lasting products such as chewables, longer-lasting flavor effects are needed.

Hydrophobic (ethyl cellulose) or hydrophilic (hydroxypropyl methylcellulose, polyvinylpyrrolidone) polymers, lipids, and sweeteners can be used as coating materials, alone or in combinations, to modify both taste and appearance, Mahmoudi adds.

In addition to preventing an unpleasant taste, Guy notes that some coatings may also include pore-formers to help promote dissolution of the drug substance to meet standard immediate-release requirements for the API. “In such formulations, a careful balance must be achieved between taste-masking and efficacy. It is therefore a rich area of development given the complexity of drug particles and granules, varying solubilities, the need to often achieve a specific location of delivery (enteric needs for instance), and excipient compatibility concerns,” he comments.

For appearance, color is most widely used to differentiate products and mask undesirable product properties. For solid dosage forms, color is applied within coatings. For liquids, water-soluble dyes are generally employed.

Ultimately, Guy contends that the choice of excipients for taste and appearance improvement comes down to the preferred dosage form and the external factors that can impact the effectiveness of the choice, which include excipient compatibility, resistance to mechanical influence (granulation and tableting), solubility, stability, etc.

Impact of need for patient-centric formulations

Because taste and appearance are important factors influencing the patient experience, it is essential for formulators to understand the preferences of different patient populations for drug formats and, within those preferred formats, taste and appearance qualities that will encourage good medication compliance. “Different patient groups based on their ages, disease states, cultures, and demographic locations may require certain taste, flavor, texture/mouthfeel, and drug product appearance properties, such as tablet size, color, and shape for solid products and the viscosity and grittiness of liquid formulations,” Tocce asserts.

Flavor companies, adds Guy, are today much more attuned to patient and consumer preferences by gender, age, and other factors. “This information can and does help formulators and brand/product managers to make smarter decisions for taste and appearance as it relates to the intended patient or therapeutic group,” he says.

In particular, Guy notes that the need to create fit-for-purpose formulations for aging populations and pediatric patients has put pressure on appearance as it relates to the size of oral solid dosage forms. For instance, important research conducted by academics and members of the European Pediatric Formulation Initiative has revealed that young children are more accepting of small or mini-tablets.

“Such a patient-centric approach definitely benefits patients, but it does present manufacturing challenges,” Guy states. “For example, it can be difficult when producing tablets that are 2 mm in diameter or smaller to achieve good flow through production equipment for APIs and excipients, which in turn impacts the ability to achieve good content uniformity and acceptable taste,” he says.

From a personalized medicine standpoint, it is also important to understand specific age-related elements of physical condition that might impact drug performance and the appropriate excipient choices. “For pediatric medicines, factors to be considered include the fat and water content along with relevant genetic information. It is a tricky area from a regulatory standpoint, but it does help guide the selection of excipients by taking into consideration their potential impacts on young developing bodies,” observes Guy.

Many excipient selection factors


Age is indeed one of the most important factors guiding excipient selection. If a medication is intended to treat a wide patient age range, Guy recommends developing modified versions formulated for subsets of the population based on reasonable age groups, such as pediatric through adult and then elderly or long-term care patients.

The first consideration, though, Guy emphasizes, is therapeutic benefit and efficacy, followed by safety, ease of use for the patient, and manufacturability. “We need to understand the target drug product profile when selecting a taste-modifying agent/approach to ensure drug performance is not negatively affected,” Mahmoudi agrees. The characteristics of the API and the desired properties of the final product directly impact excipient selection, she states.

The extent and type of unpleasant taste associated with the API (bitter, sour, irritating) and its aqueous solubility determine which excipients will be appropriate. “It can be more challenging to cover the poor taste of a highly water-soluble API than that of a less-water-soluble active,” Mahmoudi says.

In addition, the particle size and shape of the API can influence the approach for taste-masking and appearance improvement. Specifically, Mahmoudi notes that spherical particles are easier to coat than irregularly shaped particles. The dose must also be considered; it is usually easier to taste-mask a low-dose formulation.

In film-coating approaches, adds Karry, the formulator should ensure complete drug solubilization and absorption to achieve optimum bioavailability. “Doing so is especially important for reverse-enteric polymers, as they should quickly dissolve in the acidic stomach media to allow drug diffusion out of the coated core and absorption in the small intestine. Fast polymer solubilization is critical because the tablets and pellets have a short residence time in the stomach, and these polymers are not soluble in non-acidic media. In other words, if the film does not dissolve in the stomach, it will not dissolve anywhere else in the body and as such, the drug will not diffuse out of the protected core,” she explains.

Appearance factors such as shape and color can play a role in determining the correct identification and/or correct dosing material (syringe or spoon, etc.). In some cases, a certain format can address appearance concerns. For instance, Guy points to single-unit doses such as stickpacks as a potential means for enhancing identification through improved naming and ‘branding’ of the unit itself. He does stress, however, that care must be taken to ensure that these adult/senior-friendly products are child-resistant.

Experience and knowledge of patients best guides

For some excipients, such as those designed to improve API solubility, formulators have developed predictive algorithms that facilitate more rapid formulation development. Taste and appearance are more challenging, however, because often these qualities vary from one individual to another.

“Structuring data from humans and how they respond takes a great many data points and statistical analysis and remains subject to less-well-understood error knowledge. While augmented intelligence approaches can certainly help formulators make better choices sooner rather than later, there are too many unknowns, and the need for structured data is too overwhelming for good models to work at this point,” says Guy.

The fact that there is no one method that can address taste and appearance properties in every oral medication makes predictive approaches difficult, Mahmoudi agrees. She does note, however, that evaluating literature reports and patient and caregiver surveys has revealed some general “dos and don’ts” that should be followed to achieve desirable taste and drug appearance.

For example, Mahmoudi says that the use of a coating on tablets is preferred among older patients because it can help to optimize both medication identification and taste. “Elderly patients generally take multiple medications, and having tablets that are visually appealing and easy to identify and handle, such as with a score line for easy breakage and optimized dimensions and shapes that address dexterity issues, is important,” she explains.“There are more preferences towards brightly colored tablets and identification based on shape and color for different indications to avoid medication errors,” she adds.

Karry disagrees with Guy and Tocce with regard to the ability to predict bitterness and believes the process for identifying if an API is bitter has rapidly progressed in the past few years. She points to BitterDB, a free database available to formulators with more than 1000 naturally bitter and synthetic compounds and the use of machine learning algorithms trained with known bitter API molecules that can predict the bitterness of new compounds. “Based on these predictions and additional physiochemical API properties, pharmaceutical formulators can proactively plan for their choice of taste-masking technology,” Karry contends.

The use of electronic tongues, however, has not been successful to date, says Karry, and the process to test and optimize taste-masked formulations continues to be reliant on trained human panels. E-tongues are expensive instruments based on capacitance sensors that are used to rank the bitterness of formulations, but have been shown to exhibit no correlation to the results obtained by human taste panels (1).

A new formulating challenge

The use of human test panels presents its own set of challenges, including a new one that has recently arisen. A study published in 2017 by Dagan-Wiener et al. showed that 66% of drugs in clinical and experimental stages at the time were classified as bitter compounds (2). The situation remains the same today, according to Karry. Many of the drug candidates under development today, however, are different because they have much smaller differences between their therapeutic and toxic doses (NTI-drugs), she says. “For these drugs, recruiting healthy volunteers for taste panels and ensuring no side effects after evaluation of test formulations has become more complicated,” Karry remarks.

Some new technologies of note

Currently, conventional film coating and the addition of sugars, flavors, and sweeteners remain the common approaches to taste masking, but numerous other taste-masking techniques have been developed to address this challenging task, according to Mahmoudi. “Microencapsulation, high shear mixing, freeze-drying, fluid-bed coating, and spray drying have been successfully used to modify taste and making various dosage forms,” she says.

In fact, Karry notes that there is a move away from the use of flavors and sweeteners to mask bitterness because studies have shown that sucrose-sweetened medicines are associated with increased dental issues in children. Addition of acids to generate sour liquid formulations rather than bitter medicines, meanwhile, affects tooth enamel and causes dental erosion.

“For these reasons,” Karry says, “film-coating approaches are increasingly used for taste masking of bitter compounds. Commonly used polymers include methacrylate copolymers such as Kollicoat Smartseal or Eudragit E-PO since they are insoluble in saliva (pH 6.2 –7.4), but readily soluble in the stomach.”

Hot-melt extrusion and 3D printing for personalized medicines are emerging pharmaceutical technologies that Mahmoudi believes can be efficiently used to mask the taste of very bitter APIs. In particular, Mahmoudi notes that 3D printing is a powerful technique with the potential to enable the design of visually appealing tablets with modified taste.

With respect to advances in excipient technology, Mahmoudi points to the introduction of several taste-masking polymers with pH-dependent and independent solubility, new excipients such as co-processed microcrystalline cellulose (MCC) and guar gum, colloidal MCC, and many different flavors and taste-masking agents developed by excipient manufacturers as being tremendously beneficial in modifying taste and drug appearance.

For Guy, the use of taste-masking agents as ingredients, rather than simply applying a coating as a physical barrier, is transforming flavor and flavor perception. “Such an approach has allowed us to tackle ‘off-notes’ in products, particularly in nutraceutical formulations. Specifically, combining bitter-maskers with an appropriate flavor combination helps to reduce or even eliminate off-notes to a background level that is tolerable,” he says.

Orally disintegrating and dispersible solid-dose formulation have increased in popularity in recent years, creating challenges for taste masking and appearance. “It can be difficult to navigate the possible excipient choices and strategies that will ensure the desired product performance, for which there are numerous requirements and constraints,” Guy observes. “Facing challenges is not unfamiliar territory, though, and formulators do have an extensive and growing toolbox of excipients that can be applied for these and other novel oral dose forms,” he concludes.

Always remember: patients are people

When formulating any type of drug and using excipients of any kind, including
for the modification of taste and appearance, the safety, regulatory acceptance, and daily allowable intake of each excipient must clearly be considered in addition to process and cost, according to Mahmoudi. “Beyond that, patient-centric drug design is paramount. There are great taste-masking excipients/texture modifiers and techniques that should be considered from the early formulation development steps when pursuing patient-centric solutions,” she says.

In addition to ensuring safety and efficacy, Guy reiterates that the most important thing formulators must do for any drug product is to ensure that the patients and care-givers that will be using/administering the medicine will not be afraid or put-off by the nature of the drug. “It is essential to have and apply good people knowledge and consider different formulation options for different patient populations as dictated by their differing needs. Patients are people, and that must always be top of mind,” he insists.


1. Senopsys, “Case Study: Correlation of Electronic Tongue (E-Tongue) and Human Taste Panel Data,” Senopsys.com, Accessed Nov. 24, 2021.

2. A. Dagan-Wiener, et al. Sci Rep 7, 12074 (2017).

About the author

Cynthia A. Challener, PhD, in contributing editor to Pharmaceutical Technology.

Article Details

Pharmaceutical Technology
Vol. 46, No. 1
January 2022
Pages: 26–27, 45


When referring to this article, please cite it as C. Challener, “Taste and Appearance: Selecting the Right Excipients,” Pharmaceutical Technology 46 (1) 26–27, 45 (2022).