Taste assessment for paediatric drug Development: A comparison of bitterness taste aversion in children versus Naïve and expert young adult assessors.

Medicines for children often taste bitter, presenting a significant challenge to treatment compliance. However, most studies on paediatric drug development rely on adult volunteers for sensory research, and the level of expertise required from these assessors is unclear. This study aimed to address this gap by investigating perceived bitterness aversion to taste strips impregnated with different concentrations of quinine hydrochloride in 439 school-aged children. Expert (n = 26) and naïve (n = 65) young adult assessors evaluated quinine solutions as well as taste strips, for methodological bridging purposes. All assessors differentiated the aversiveness of the taste strips in a dose dependent manner. Younger children aged 4-8 years had difficulty discriminating higher bitter concentrations, whereas pre-adolescents 9-11 years and naive adults showed better discrimination at the top of the scale. Naive assessors showed similar bitter perception as children. However, the results were slightly different between strips and solution in adults. These findings highlight the key role that adult panels can play in paediatric formulation development. Taste strips show promise as a safe and pragmatic tool for sensory pharmaceutical evaluations, though further studies are warranted to establish the relationship between age and hedonic taste perception using compounds with diverse physicochemical and sensory qualities.

A Guide to Best Practice in Sensory Analysis of Pharmaceutical Formulations.

It is well established that treatment regime compliance is linked to the acceptability of a pharmaceutical formulation, and hence also to therapeutic outcomes. To that end, acceptability must be assessed during the development of all pharmaceutical products and especially for those intended for paediatric patients. Although acceptability is a multifaceted concept, poor sensory characteristics often contribute to poor patient acceptability. In particular, poor taste is often cited as a major reason for many patients, especially children, to refuse to take their medicine. It is thus important to understand and, as far as possible, optimise the sensory characteristics and, in particular, the taste/flavour/mouthfeel of the formulation throughout the development of the product. Sensory analysis has been widely practiced, providing objective data concerning the sensory aspects of food and cosmetic products. In this paper, we present proposals concerning how the well-established principles of sensory analysis can best be applied to pharmaceutical product development, allowing objective, scientifically valid, sensory data to be obtained safely. We briefly discuss methodologies that may be helpful in reducing the number of samples that may need to be assessed by human volunteers. However, it is only possible to be sure whether or not the sensory characteristics of a pharmaceutical product are non-aversive to potential users by undertaking sensory assessments in human volunteers. Testing is also required during formulation assessment and to ensure that the sensory characteristics remain acceptable throughout the product shelf life. We provide a risk assessment procedure to aid developers to define where studies are low risk, the results of a survey of European regulators on their views concerning such studies, and detailed guidance concerning the types of sensory studies that can be undertaken at each phase of product development, along with guidance about the practicalities of performing such sensory studies. We hope that this guidance will also lead to the development of internationally agreed standards between industry and regulators concerning how these aspects should be measured and assessed throughout the development process and when writing and evaluating regulatory submissions. Finally, we hope that the guidance herein will help formulators as they seek to develop better medicines for all patients and, in particular, paediatric patients.

Responsive Sensory Evaluation to Develop Flexible Taste-Masked Paediatric Primaquine Tablets against Malaria for Low-Resource Settings.

Primaquine is an important antimalarial drug for malaria transmission blocking and radical cure, but it is not currently available in child-friendly formulations in appropriate doses. Adult-strength tablets are often crushed and dissolved in water to obtain the required dose, which exposes the drug's bitter taste. As part of the developing paediatric primaquine (DPP) project, this study adopted a responsive sensory pharmaceutics approach by integrating real-time formulation development and pre-clinical taste assessment to develop palatable, flavour-infused primaquine tablets. A design of experiment (DoE) approach was used to screen different taste-masking agents and excipient blends with trained, expert sensory assessors, with quinine hydrochloride as a model bitter tastant. The taste-masking efficacy of selected prototype formulation blends was validated with naïve assessors using the highest 15 mg primaquine dose. The mean bitterness intensity rating, measured on a discrete 11-point scale, was halved from 7.04 for the unflavoured control to 2.74-3.70 for the formulation blends. Sucralose had the biggest impact on bitterness suppression and improving palatability. Two different flavouring systems have been developed, and their acceptability in paediatric patients will be assessed as part of upcoming validation field clinical trials in Africa.

Rational and practical considerations to guide a target product profile for patient-centric drug product development with measurable patient outcomes - A proposed roadmap.

The increasing awareness of acceptability and usability of pharmaceutical drug products by the patient as a key quality requirement continues to drive need for integrating patient centric drug product design into the pharmaceutical development process. The complex matrix of multiple drug product related decisions during the early drug development process often limits patient-centric drug product (PCDP) design options in the final commercial drug product development phase. To integrate the specific needs and perspectives of patients into drug development and product design process, a rational approach integrated into the complex development matrix is required from the start and weighs product development decision options accordingly. The aim of this work was to develop a roadmap for PCDP design in a multidisciplinary approach that leads to better usability, adherence and acceptance of the drug by patients via early integration into the development matrix. The proposed rational approach is based upon regulatory requirements and lessons learned from pediatric and geriatric drug development.

A review on octenyl succinic anhydride modified starch-based Pickering-emulsion: Instabilities and ingredients interactions.

Pickering emulsions endow attractive features and a wide versatility in both food and nonfood fields. In the last decades, a noticeable interest has emerged toward the use of octenyl succinic anhydride (OSA)-starch to improve the long-term stability in such systems. In this review, instabilities were pointed out, where a new kinetic equilibrium was observed in Pickering emulsions assigned to migration and size variations of particles. These features were monitored using rheological measurements to understand microstructure and droplets mobility. The elastic modulus (G'), the viscous modulus (G″), and tan(δ) values were attributed to the transition from solid to fluid and assigned to the instability of the formulation regardless of the type of the system configuration. The novelties in using OSA-modified starch, were also exposed. The chemical modification of starch decreased creaming for months. Interaction between OSA-modified starches and some ionic components (potassium, magnesium, and calcium) as well as hydrocolloids and proteins reduced creaming and coalescence due to dense interfacial film. Furthermore, the key parameters (oil fraction, fatty acids composition, oxidative stress oil polarity, and oil viscosity) that govern oil phase in Pickering emulsion, were analyzed. These parameters were found to be positively correlated to the stability of Pickering emulsions.

Proposed Tool to Compare and Assess the Applicability of Taste Assessment Techniques for Pharmaceuticals.

Palatability is amongst the most important determinants of whether or not a child will take a medicine. In order to increase concordance with treatment regimens it is often necessary to utilise a range of formulation techniques to improve the palatability of medicines. These can include selecting a different molecule or version of a molecule (such as a different polymorph or salt form), various taste masking techniques and/or the inclusion of flavours and sweeteners. In order to be able to understand the taste of the Active Pharmaceutical Ingredient (API) and to validate the formulation approach used, it is necessary to be able to use the most reliable taste evaluation method possible. Multiple in vivo and in vitro methods exist nowadays or are proposed in the literature but are often little understood by the pharmaceutical product development community. In particular, different methods may be more relevant at different stages of product development. The aim of this article is to propose a tool to guide the selection of the most appropriate method for the desired evaluation. A spreadsheet-based tool is proposed that is designed to allow the systematic assessment of the applicability of any taste assessment technique existing or new to the users proposed application. A series of criteria are defined that will allow the user to assess the analytical, usability and availability factors for the technique that is being considered. Such a systematic review will help the user to understand the benefits and risks of using each methodology for that application. The use of the tool is illustrated based on currently available data and literature. As new/existing methods are developed/improved, the outcomes of the tool may change.

Medicines Acceptability in Hospitalized Children: An Ongoing Need for Age-Appropriate Formulations.

Although knowledge on medicine acceptability remains fragmented, this multi-faceted concept has emerged as a key factor for compliance in pediatrics. In order to investigate the acceptability of medicines used in the University Medical Centre Ibn Sina (CHIS) of Rabat, Morocco, an observational study was conducted. Using a multivariate approach integrating the many aspects of acceptability, standardized observer reports were collected for 570 medicine intakes in patients up to the age of 16, then analyzed on a reference framework. Tablets appeared to be well accepted in children greater than 6 years old, but were crushed/dissolved for 90% of the 40 children aged from 3 to 5, and 100% of the 38 patients younger than 3. Moreover, the prescribed dose was fully taken for only 52% and 16% of these younger children, respectively. Despite this, tablets represented 24% of evaluations in children from 3 to 5 and 20% in infants and toddlers. Oral liquid preparations appeared to be better accepted than tablets in preschoolers, but not for those under 3. Overall, these findings highlight the lack of suitable alternatives for the younger children, especially for formulations of antiepileptics, antithrombotic, and psycholeptic agents in the local context.

Combining sensory and texturometer parameters to characterize different type of cosmetic ingredients.

INTRODUCTION: Sensory properties have a great importance for cosmetics and personal care products. If literature permits to consult articles comparing different formulations on their sensory attributes, there are only a few articles concerning ingredients. OBJECTIVE: The overall objective of this study was to carry out an original study combining the sensory evaluation of different natures of ingredients, in order to initiate a sensory data set that could help researchers to identify differentiating sensory characteristics, as well as initiating a comparison between sensory data and texturometer instrumental measurements. METHODS: Oils, glycolic extracts, butter and starch were evaluated according to descriptive sensory analysis methodology with the help of panel of 25 experts. In order to compare responses obtained from the panel to instrumental measurements, texture analyzes were performed in compression traction model. RESULTS: Significant differences were detected in ten of the eleven evaluated sensory attributes, indicating that ingredients have distinct sensory profiles. The mainly discriminative attributes for the analyzed ingredients were: gloss, opacity, fluidity, freshness, whitening and oily residue. The oils are mostly related to oily residue and slipperiness while extracts are mostly related to gloss, fluidity and freshness attributes. Both Tapioca Starch and Shea Butter were related to non-fluidity, opacity, and Tapioca Starch was related to freshness too. This study was completed by a texturometer analysis which lead to show the opposite correlation between the sensory attribute fluidity and the consistent index.

INTRODUCTION: Les propriétés sensorielles ont une grande importance pour les cosmétiques et les produits de soins. Si la littérature permet de consulter des articles comparant différentes formulations sur leurs attributs sensoriels, il n'y a que quelques articles concernant les ingrédients. OBJECTIF: L'objectif global de cette étude était de réaliser une étude originale combinant l'évaluation sensorielle de différentes natures d'ingrédients, afin d'initier un ensemble de données sensorielles qui pourrait aider les chercheurs à identifier les caractéristiques sensorielles discriminantes, ainsi qu'à initier une comparaison entre données sensorielles et mesures instrumentales du texturomètre. MÉTHODES: Les huiles, les extraits glycoliques, le beurre et l'amidon ont été évalués selon la méthodologie d'analyse sensorielle descriptive avec l'aide d'un panel de 25 experts. Afin de comparer les réponses obtenues à partir du panel aux mesures instrumentales, des analyses de texture ont été effectuées avec un texturométre selon la méthode traction-compression. RÉSULTATS: Des différences significatives ont été détectées sur dix des onze attributs sensoriels évalués, indiquant que les ingrédients ont des profils sensoriels distincts. Les attributs principalement discriminants pour les ingrédients analysés étaient : la brillance, l'opacité, la fluidité, la fraîcheur, le blanchiment et les résidus huileux. Les huiles sont principalement liées aux descripteurs résidus huileux et glissant tandis que les extraits sont principalement liés aux attributs de brillance, de fluidité et de fraîcheur. L'amidon de tapioca et le beurre de karité étaient tous deux liés à la non-fluidité, l'opacité et l'amidon de tapioca était également lié à la fraîcheur. Cette étude a été complétée par une analyse texturométrique qui a montré la corrélation opposée entre le descripteur sensoriel fluide et l'indice de consistance.

Impact of sampling and DNA extraction methods on skin microbiota assessment.

The skin microbiota is characterized by high intra- and inter-variability among individuals, due to a multitude of intrinsic and extrinsic parameters such as genetics, lifestyles or pollution. This variability may be heightened due to sampling method as the skin is a multilayer organ and its outermost layer consists of dead cells. In order to investigate this biological variability in a reproducible way, we studied how sampling procedure and DNA extraction methods influence the qualitative and quantitative gathering of bacterial communities. Here, we tested a new sampling procedure that consists in exerting a slight abrasion (scrubbing) on the skin prior to swabbing and extracting DNA in order to remove squames and access deeper ecological niches. Scrubbed and non-scrubbed samples were collected from a panel of six volunteers, and four DNA extraction methods were performed on the samples. The abundance, diversity and structure of the bacterial communities were measured using qPCR technics and 16S rDNA gene-metabarcoding. Bacterial community abundance was significantly impacted by the DNA extraction method (in favor of a method designed for tissues) but not by sampling procedure, as scrubbing does not increase bacterial biomass gathered. Bacterial α- and ß-diversities were both affected by DNA extraction methods and sampling procedure. Scrubbing reveals different microbial composition by gathering bacteria living in deeper skin layer, resulting in a lower intra-personal variability. The taxonomic analysis showed that more bacteria belonging to anaerobes groups were present in scrubbed samples. We conclude that DNA extraction methods designed for tissue are not necessarily associated with high qualitative efficiency and slight scrubbing prior DNA extraction reduces intrapersonal variability and give access to a new microbial diversity.

Standardised evaluation of medicine acceptability in paediatric population: reliability of a model.

OBJECTIVES: Our novel tool to standardise the evaluation of medicine acceptability was developed using observational data on medicines use measured in a paediatric population included for this purpose (0-14 years). Using this tool, any medicine may be positioned on a map and assigned to an acceptability profile. The present exploration aimed to verify its statistical reliability. METHODS: Permutation test has been used to verify the significance of the relationships among measures highlighted by the acceptability map. Bootstrapping has been used to demonstrate the accuracy of the model (map, profiles and scores of acceptability) regardless of variations in the data. Lastly, simulations of enlarged data sets (×2; ×5; ×10) have been built to study the model's consistency. KEY FINDINGS: Permutation test established the significance of the meaningful pattern identified in the data and summarised in the map. Bootstrapping attested the accuracy of the model: high RV coefficients (mean value: 0.930) verified the mapping stability, significant Adjusted Rand Indexes and Jaccard coefficients supported clustering validity (with either two or four profiles), and agreement between acceptability scores demonstrated scoring relevancy. Regarding enlarged data sets, these indicators reflected a very high consistency of the model. CONCLUSIONS: These results highlighted the reliability of the model that will permit its use to standardise medicine acceptability assessments.

Standardized method to assess medicines' acceptability: focus on paediatric population.

OBJECTIVES: The purpose of this article was to present an original standardized tool assessing the medicine's acceptability whichever their characteristics and the patient features. METHODS: An acceptability map was built with objective measures from medicine use assessments collected in real-life conditions. Multiple correspondence analysis (MCA) was used for the mapping process. Hierarchical classification on the principal components (HCPC) of the MCA was performed for the clustering process corresponding to distinct acceptability profiles. KEY FINDINGS: The results presented here focus on 234 evaluations issued from the paediatric population and gathered in four clusters: 'well-accepted' (50%), 'accepted' (19%), 'poorly accepted' (25%) and 'not accepted' medicines (6%). The first one was characterized by a dose fully taken, in a short time, with a patient's positive reaction; the second by a longer administration time, a neutral reaction and the use of methods to achieve administration (reward, divided dose). Differentiation between the two last clusters was, respectively, originated by a required dose partially taken or not taken. CONCLUSIONS: The acceptability profile of each medicine can be evaluated with the map position of the related patient's assessments barycentre. This tool should satisfy expectations in terms of methods for appropriate acceptability evaluation and standardized comparison among medicines.