Poor-tasting pediatric medicines: part 2. Exploring caregiver and healthcare provider values and preferences for a novel taste-blocker product to improve acceptability

Abstract

Introduction: Improving the palatability of bitter-tasting medication for pediatric populations has long presented a challenge. Taste blockers are being researched as a potential solution; however, end-user perspectives and needs related to this concept have not been explored. The objectives of this research were 1) to understand current experiences of administering bitter-tasting medication; 2) the evaluation of a consumer-targeted product profile (CTPP) for a taste blocker including attributes such as form and duration of action; and 3) whether there is a need to support improved acceptability and adherence with a taste blocker taken before the bitter-tasting medication.

Methods: Our study consisted of simultaneous qualitative and quantitative phases, involving caregivers and healthcare providers with experience administering medications to children aged 2–17 years. Qualitative research was conducted with 120 caregivers and 92 healthcare providers using a range of methods. Focus groups (FGs) were conducted in Kenya, Nigeria and Zimbabwe (grouped as Sub-Saharan Africa (SSA) but not intended to be representative of the region as a whole) with caregivers of children who had taken medication for HIV, TB, pneumonia, or malaria (including for seasonal prevention) within the past 6 months. Telephone in-depth interviews (TDIs) were conducted with caregivers of children with chronic illnesses in the United States. Face-to-face in-depth interviews (IDIs) and TDIs were conducted with healthcare providers. The quantitative part of the study was conducted with n = 1,815 caregivers and n = 859 healthcare providers using face-to-face computer-assisted interviews (CAPI) in SSA, and via online panel research in the United States A CTPP was used as the stimulus for discussion. Participants were asked about their experiences in giving bitter-tasting medication to their children or patients, their perceptions of and willingness to try a taste blocker, and their preferences for specific product attributes.

Results: Participants described how bitter-tasting medications create challenges in multiple areas: for caregivers, children, their daily life and routines, healthcare providers, and children’s perceptions of healthcare. In SSA, 28.9% of caregivers reported that their children always or regularly refused medication due to bitter taste, while 57.9% reported this in the United States. Another 36.2% and 29.1% respectively experienced this sometimes or occasionally. Over 80% of providers in all countries stated that bitter taste impacts adherence to both long and short-term medication. The preferred attributes of the taste blocker were a sweetened and flavored lollipop form with a maximum total duration of up to approximately 1h, and with a total taste block achieved as soon as possible. Overall, responses to the concept of the taste blocker were positive from caregivers and providers, with a perception that it would make administering bitter-tasting medication easier. Over 90% were positive about using or prescribing the taste blocker in SSA, while in the United States, over 90% of caregivers were positive about using it, as were over 70% of providers about prescribing it. Concerns centered around the duration of the absence of the sense of taste, and the effects this might have on children’s appetite; there were also concerns that repeated taste blocking might have a long-term impact on children’s sense of taste.

Conclusion: The results of the study indicate that there is a high perceived need for a taste blocker to aid in administering bitter-tasting pediatric medication. Concerns around duration and potential impact of long-term use must be addressed.

Introduction

Although the burden of communicable diseases such as human immunodeficiency virus (HIV), malaria, and respiratory infections including tuberculosis (TB) has broadly declined over recent decades, there is still a high burden in low-middle-income-countries (LMICs), particularly in Sub-Saharan Africa (SSA) and South Asia. Moreover, the prevalence of communicable diseases, such as HIV, malaria, and TB, is disproportionately higher among children, particularly those under the age of five, compared to adults (Our World in Data, 2024). For example, pneumonia is reported to cause more deaths among children than any other infectious disease, causing 700,000 deaths of children under the age of five worldwide each year (UNICEF, 2024a), and an estimated 2.58 million children worldwide were living with HIV in 2022, with an estimated 100,000 AIDS-related deaths in children (UNICEF, 2024b). Globally, there were an estimated 263 million cases of malaria in 2023 and 597,000 deaths, with 94% of these cases (246 million) and 95% of these deaths (569,000) occurring in the WHO’s African region, of which children under 5 years accounted for approximately 76% of the deaths (World Health Organization, 2024b). The global TB incidence rate (new cases per 100,000 population per year) is estimated to have increased by 4.6% between 2020 and 2023, from 129 in 2020 to 134 in 2023, and in 2023 there were an estimated 1.3 million cases of TB among children and young adolescents (aged 0–14 years), equivalent to 12% of the estimated total (World Health Organization, 2024a). Despite the overall global rate of availability of essential medicines for children increasing slightly over recent years, the availability rate for systemic anti-infectives is reported to be low (Shi et al., 2023). The data above therefore underscores the critical need for increasing and ensuring consistent and equitable access to essential medications for children, particularly those under five, in LMICs.

It should be noted that in addition to maximizing access to medications to treat and prevent these diseases, it is important that medicines are age-appropriate and acceptable for the intended patient population. Patient acceptability is likely to impact patient medication adherence and is determined by the characteristics of both the product and user, with palatability being considered to be one of the main elements of patient acceptability of oral pediatric medicinal products (EMA, 2012). Indeed, it has been reported that poor taste is a common barrier to oral medicine administration in children, which may lead to lack of adherence and sub-optimal treatment outcomes (Lin et al., 2011; Mennella et al., 2015; Venables et al., 2015; Elgammal et al., 2023). For example, the poor taste of anti-retroviral medications such as ritonavir and nelfinavir has been reported to be a barrier to adherence, with a lack of adherence being associated with poor virologic response to therapy (Davies et al., 2008; Van Dyke et al., 2002).

Challenges associated with poor-tasing pediatric medicines are not limited to LMICs. For example, infectious diseases in children continue to be a major public health problem in the United States of America (United States) (Goto et al., 2016), and poor palatability, incomplete dosing and sub-optimal ease of use have been reported for some antibiotic and anti-pyretic/analgesic medications that are commonly used to treat such conditions (Cifaldi et al., 2004; Cohen et al., 2009; Klingmann et al., 2022; Smith et al., 2013). Furthermore, it has been estimated that approximately 25% of children and adolescents in the United States are affected by chronic conditions that require medication (Miller et al., 2016).

Many active pharmaceutical ingredients (APIs) have a bitter taste, and various taste-masking techniques have been developed and applied to formulations to improve their palatability (Ayenew et al., 2009; Kaushik and Dureja, 2014; Walsh et al., 2014; AL-Japairai et al., 2023; Hu et al., 2023). The perception of taste is through the interaction of molecules with taste receptors, and taste-masking strategies include the obscuration of taste via the addition of sweetening and/or flavoring agents, and the creation of a barrier between the API molecules and taste receptors, for example, by complexation or application of a coating (Ayenew et al., 2009; Kaushik and Dureja, 2014; Walsh et al., 2014; AL-Japairai et al., 2023; Hu et al., 2023).

Improving the palatability of APIs is likely to enhance patient acceptability and adherence, particularly in pediatric populations where taste remains a significant barrier to effective treatment (Baguley et al., 2012). Increased adherence to medications can directly translate into better health outcomes, reducing the disease burden and improving quality of life (Claxton et al., 2001; World Health Organization, 2003). Therefore, continued research and development into advanced taste-masking techniques and bitterness-blocking technologies are not only justified but essential for optimizing therapeutic efficacy and addressing global health challenges.

There has been increasing interest in the human taste pathway and the identification, development and use of compounds that can block the perception of bitterness at a molecular level, so called “bitter blockers”. Examples of commercially available and “generally regarded as safe” (GRAS) compounds that have been reported to show evidence of bitter blocking include sodium salts such as sodium acetate, sodium gluconate and sodium chloride, citric acid and adenosine 5′ monophosphate (Andrews et al., 2021). The perception of bitter taste is mediated via a family of around 25 G-protein coupled receptors (GPCR), the TAS2Rs. When a bitter compound interacts and binds with one or more TAS2Rs, this leads to the release of neurotransmitter that culminates in the activation of an afferent nerve fiber (usually the gustatory nerve) that transmits a signal to the brain (Mennella and Beauchamp, 2008; Mennella et al., 2013). Each TAS2R receptor is likely to recognize structurally similar compounds, and many APIs interact with multiple bitter receptors, leading to the need to apply more than one bitter blocker to fully block the taste. Indeed, the efficacy of a bitter blocker is compound specific and it has been reported that age may affect bitter blocking, potentially being less effective in children compared to adults (Mennella and Beauchamp, 2008; Mennella et al., 2014; Andrews et al., 2021; Flammer et al., 2024). Furthermore, there is some genetic variation in taste receptors which may lead to inter-subject variability in bitter blocking efficacy (Mennella et al., 2013; Nguyen et al., 2024). An alternative and emerging approach to blocking bitterness by antagonizing bitter taste receptors is via the prevention of the nerve signals that generate taste sensation from reaching the brain, although this would also affect other taste sensations such as sweet, sour, salt and umami (Flammer et al., 2024).

The blocking of bitterness taste perception using bitter or taste blockers may potentially be more effective compared to conventional methods of taste-masking, depending on the properties of the API and approach used. It may, therefore, offer a means by which the palatability and acceptability of a pediatric medicine can be improved, resulting in improved adherence and clinical outcomes in pediatric populations (Baguley et al., 2012; Claxton et al., 2001).

It is important to understand patient and caregiver experiences of administering and taking pediatric medicines and their perceptions of potential product development solutions to mitigate any challenges they face, to facilitate the development and administration of age-appropriate and acceptable pediatric medicines.

This research is complemented by an accompanying scoping review examining the impact of poor tasting pediatric medicines on patient acceptability, medication adherence, and treatment outcomes (Ranmal et al., 2024). The review highlights the global nature of the issue, which was found to affect children of all ages, with more than 150 unpalatable drugs identified across over 70 different disease areas. These findings underscore the need for more effective and universal taste-masking solutions such as a taste blocker.

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Moushira El-Sahn, Rose Elliott, Mona El-Sahn, Izaak Lucas, Karen Kong, Jennifer Walsh and Jeff Lucas, Poor-tasting pediatric medicines: part 2. Exploring caregiver and healthcare provider values and preferences for a novel taste-blocker product to improve acceptability, ORIGINAL RESEARCH article, Front. Drug Deliv., 22 April 2025, Sec. Drug Delivery for Special Patient Populations, Volume 5 – 2025 | https://doi.org/10.3389/fddev.2025.1555522