Dosage Forms Suitability in Pediatrics: Acceptability of Analgesics and Antipyretics in a German Hospital

Klingmann, Viviane; Vallet, Thibault; Münch, Juliane; Stegemann, Robin; Wolters, Lena; Bosse, Hans Martin; Ruiz, Fabrice

doi:10.3390/pharmaceutics14020337

Cited by 13 publications

(11 citation statements)

References 32 publications

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“…Acceptability of drugs is crucial for children due to inherent characteristics of this population including swallowing difficulties and strong taste sensitivity [ 18 , 19 , 20 ]. Acceptability as defined by drug agencies includes the pharmaceutical characteristics of the medicine such as palatability, size and shape [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmaceutical Oral Formulation of Methionine as a Pediatric Treatment in Inherited Metabolic Disease

et al. 2023

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L-Methionine (Met) is an essential alpha-amino acid playing a key role in several metabolic pathways. Rare inherited metabolic diseases such as mutations affecting the MARS1 gene encoding methionine tRNA synthetase (MetRS) can cause severe lung and liver disease before the age of two years. Oral Met therapy has been shown to restore MetRS activity and improve clinical health in children. As a sulfur-containing compound, Met has a strongly unpleasant odor and taste. The objective of this study was to develop an optimized pediatric pharmaceutical formulation of Met powder, to be reconstituted with water, to obtain a stable oral suspension. Organoleptic characteristics and physicochemical stability of the powdered Met formulation and suspension were evaluated at three storage temperatures. Met quantification was assessed by a stability-indicating chromatographic method as well as microbial stability. The use of a specific fruit flavor (e.g., strawberry) with sweeteners (e.g., sucralose) was considered acceptable. No drug loss, pH changes, microbiological growth, or visual changes were observed at 23 ± 2 °C and 4 ± 2 °C with the powder formulation for 92 days, and the reconstituted suspension for at least 45 days. The developed formulation facilitates the preparation, administration, the dose adjustment and palatability of Met treatment in children.

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Section: Discussionmentioning

confidence: 99%

Pharmaceutical Oral Formulation of Methionine as a Pediatric Treatment in Inherited Metabolic Disease

et al. 2023

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“…Starting in 2009 with a first prospective uncontrolled, single-dose study with a single 3 mm mini-tablet in 100 children aged 2 to 6 years, [ 14 ] used an observation score distinguishing between “swallowed,”” chewed,” “spat out,” or “refused to take”. In further studies by other groups, assessment methods included observations by parents, care givers, and patients; different assessment scores were based on opinions or observation, visual analogue scales, or by trained investigators under highly standardized conditions and video observation [ 4 , 15 , 16 ]. Different parameters such as acceptability, swallowability, and palatability were assessed after formulation administration together with different vehicles like drinks or soft food.…”

Section: Discussionmentioning

confidence: 99%

A Composite Endpoint for Acceptability Evaluation of Oral Drug Formulations in the Pediatric Population

Wargenau¹,

Reidemeister

Klingmann

et al. 2022

Ther Innov Regul Sci

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Introduction A medicine’s acceptability is likely to have significant impact on pediatric adherence. The importance is underlined in EMA and FDA guidance on this topic where investigation of acceptability is stated as a regulatory expectation. Demonstrating acceptability can be challenging given there is no globally recognized definition and no standardized testing methodology or assessment criteria. Palatability and swallowability are generally recognized as important elements of acceptability, and this work proposes a definition of acceptability using these elements to give a composite endpoint for acceptability for pediatric subjects across all age ranges. Methods This composite acceptability endpoint is based on validated assessment methods for swallowability and palatability in children of different age groups using different galenic placebo formulations, in line with criteria proposed by EMA for assessing acceptability in children from newborn to 18 years of age. Data from two studies investigating mini-tablets, oblong tablets, orodispersible films, and syrup were analyzed to establish the validity, expediency, and applicability of the suggested composite acceptability assessment tool. Results The new composite endpoint is an efficient and suitable way to distinguish preferences of oral formulations: Mini-tablets and oblong tablets had significantly better acceptability than syrups and orodispersible films. Conclusion Since the suggested acceptability criteria takes both swallowability and palatability into account as composite endpoint, it is highly sensitive to detect acceptability differences between oral formulations. It is a well-defined valid approach, which meets regulatory requirements in an appropriate and comprehensive manner and may in future serve as a pragmatic, standardized method to assess and compare acceptability of pediatric formulations with active substances.

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“…For younger children, it may be necessary to use trained observers or automated facial recognition methodologies to assess the child’s reaction from their facial responses and their action (e.g., whether they grimace or spit out the sample) [ 71 , 72 ]. Where the sample can actually be taken by a child, the CAST system [ 73 ], which has recently received a letter of support from the EMA for acceptability testing [ 74 ], can provide a structured, multifaceted assessment of overall sample acceptability [ 75 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. Implementing an acceptability testing strategy as soon as possible in product development is important to better understand the many aspects—not limited to sensory aspects—of this multi-faceted concept.…”

Section: Human Sensory Analysismentioning

confidence: 99%

A Guide to Best Practice in Sensory Analysis of Pharmaceutical Formulations

Clapham,

Belissa,

Inghelbrecht

et al. 2023

Pharmaceutics

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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.

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Dosage Forms Suitability in Pediatrics: Acceptability of Analgesics and Antipyretics in a German Hospital

Cited by 13 publications

References 32 publications

Pharmaceutical Oral Formulation of Methionine as a Pediatric Treatment in Inherited Metabolic Disease

Pharmaceutical Oral Formulation of Methionine as a Pediatric Treatment in Inherited Metabolic Disease

A Composite Endpoint for Acceptability Evaluation of Oral Drug Formulations in the Pediatric Population

A Guide to Best Practice in Sensory Analysis of Pharmaceutical Formulations

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