Acceptability of Uncoated Mini-Tablets in Neonates—A Randomized Controlled Trial

Klingmann, Viviane; Seitz, Annika; Meißner, Thomas; Breitkreutz, Jörg; Moeltner, Andreas; Bosse, Hans Martin

doi:10.1016/j.jpeds.2015.07.010

Cited by 120 publications

(85 citation statements)

References 7 publications

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“…Recent studies assessing the acceptability and swallowability of placebo mini-tablets have been a notable emergence in the field, particularly as a dosage form for neonates and infants (Klingmann et al, 2013, Klingmann et al, 2015, Thomson et al, 2009, van Riet-Nales et al, 2013, Kluk et al, 2015. An important objective of 235 the CALF study was to determine acceptability and perceptions of these dosage forms in older children, since very little is reported in the literature.…”

Section: Novel Dosage Formsmentioning

confidence: 99%

Age-appropriate and acceptable paediatric dosage forms: Insights into end-user perceptions, preferences and practices from the Children’s Acceptability of Oral Formulations (CALF) Study

Ranmal¹,

Cram

Tuleu³

2016

International Journal of Pharmaceutics

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A lack of evidence to guide the design of age-appropriate and acceptable dosage forms has been a longstanding knowledge gap in paediatric formulation development. The Children's Acceptability of Oral Formulations (CALF) study captured end-user perceptions and practices with a focus on solid oral dosage forms, namely tablets, capsules, chewables, orodispersibles, multiparticulates (administered with food) and mini-tablets (administered directly into the mouth). A rigorous development and testing phase produced age-adapted questionnaires as measurement tools with strong evidence of validity and reliability. Overall, 590 school children and adolescents, and 428 adult caregivers were surveyed across hospitals and various community settings. Attitudes towards dosage forms primarily differed based on age and prior use. Positive attitudes to tablets and capsules increased with age until around 14 years. Preference was seen for chewable and orodispersible preparations across ages, while multiparticulates were seemingly less favourable. Overall, 59.6% of school children reported willingness to take 10mm diameter tablets, although only 32.1% of caregivers perceived this size to be suitable. While not to be taken as prescriptive guidance, the results of this study provide some evidence towards rational dosage form design, as well as methodological approaches to help design tools for further evaluation of acceptability within paediatric studies.

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Section: Novel Dosage Formsmentioning

confidence: 99%

Age-appropriate and acceptable paediatric dosage forms: Insights into end-user perceptions, preferences and practices from the Children’s Acceptability of Oral Formulations (CALF) Study

Ranmal¹,

Cram

Tuleu³

2016

International Journal of Pharmaceutics

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“…In summary, we have found that 4-mm uncoated mini-tablets can be used successfully in children from 1 year of age (46). In addition, Klingmann et al showed that smaller 2-mm minitablets can be used in infants from 6 months of age, whereas 2 mm rapidly dissolving mini-tablets can be used as early as in the pre-term age (47,48). These studies actually indicated that mini-tablets are equally or even better accepted than oral Table I.…”

Section: Mini-tabletsmentioning

confidence: 72%

Paediatric Drug Development and Formulation Design—a European Perspective

Riet‐Nales

Kozarewicz²,

Aylward

et al. 2016

AAPS PharmSciTech

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Abstract.The availability of licensed paediatric drugs is lagging behind those for adults, and there is a lack of safe formulations in suitable doses that children are able and willing to take. As a consequence, children are commonly treated with off-label or unlicensed drugs. As off-label and unlicensed drug use are associated with a greater risk for harm than on-label drug use, a range of global initiatives have been developed to realize Bbetter^medicines for children. This review describes the challenges and achievements of the European Union to realize this goal, with a focus on paediatric drug development and formulation design. In 2007, a European Paediatric Regulation was installed enforcing companies to consider children in the early development of drugs with a new drug substance, for a new indication or with a new route of administration. The Regulation, e.g. requires companies to develop a paediatric investigation plan discussing the proposed clinical trials in children of different ages and the formulations for future marketing. Since 2013, the pharmaceutical design of any newly marketed paediatric drug should comply with the BGuideline on the Pharmaceutical Development of Medicines for Paediatric Use.^Companies should, e.g. justify the route of administration, dosage form, formulation characteristics, safety of excipients, dosing frequency, container closure system, administration device, patient acceptability and user information. In this review, the guideline's key aspects are discussed with a focus on novel formulations such as mini-tablets and orodispersible films, excipients with a potential risk for harm such as azo dyes and adequate user instructions.

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“…Several studies have since investigated the opinion of children about oral formulations, and also studied in an experimental setting how the young children are able to take different formulations, particularly the new minitablets (diameter 2-5 mm) [4][5][6][7]. In a randomised crossover study of 306 children aged 6 months to 6 years the children accepted a 2 mm placebo mini-tablet significantly better than a sweet syrup (placebo) and were also able to swallow the mini-tablets more reliably than the syrup, including those in the age group of 6 months to 1 year [5].…”

Section: Ceylon Medical Journalmentioning

confidence: 99%

Time to change the paradigm of children’s medicines from liquid formulations to flexible solid oral dosage forms

Hoppu

2016

Ceylon Med. J.

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Time to change the paradigm of children's medicines from liquid formulations to flexible solid oral dosage formsWorldwide, people prefer a liquid formulation when paediatric medicines have to be given orally. The syrups and suspensions can be dosed flexibly by increasing the volume with age and weight of the child. We believe that young children can swallow liquids better than solids and prefer to take a sweet tasting liquid medicine. Simply liquid medicines are what children choose if they are given the chance -or at least that is what we adults think. When new innovative medicines are developed for use in children, the global pharmaceutical industry usually develops a liquid formulation for children if the medicine is to be given orally. In rich countries liquid formulations for oral medicines continue to be the rule.In resource limited settings (RLS) age appropriate paediatric formulations for children are not commonly available [1,2]. If what the pharmaceutical industry develops for children are liquid formulations, then one could think that the lack of paediatric medicines in RLS could be just a consequence of the general lack of availability of children's medicines in those settings. But what if the domination of liquid oral formulations as the perceived first choice for children is in fact also a cause and not only a consequence of the problem of poor availability of age appropriate paediatric medicines in RLS? Indeed, liquid oral formulations possess problematic characteristics particularly relevant in RLS [1]. Logistics of liquid oral formulations are complicated by increased bulk and commonly need cold-chain, problems for both the professional of bulk transport, and for the family who has to carry the child's medicines home. From a pharmaceutical development and manufacturing point of view, liquid medicines are problematic in many ways. Taste-masking is challenging, liquid formulations require more excipients than solid ones, and some excipients may not be suitable for children. Importantly, liquid formulations are more expensive to produce than solid dosage forms. The higher costs of production and logistics make liquid medicines more expensive than medicines in solid formulations. A switch to solid oral paediatric formulations would be a way to improve availability of paediatric medicines, if only the children would accept them and be able to swallow them.May be we should ask the children! That is exactly what we did in Helsinki in 1999 when we interviewed 150 children who were 3-7 years old andThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Acceptability of Uncoated Mini-Tablets in Neonates—A Randomized Controlled Trial

Cited by 120 publications

References 7 publications

Age-appropriate and acceptable paediatric dosage forms: Insights into end-user perceptions, preferences and practices from the Children’s Acceptability of Oral Formulations (CALF) Study

Age-appropriate and acceptable paediatric dosage forms: Insights into end-user perceptions, preferences and practices from the Children’s Acceptability of Oral Formulations (CALF) Study

Paediatric Drug Development and Formulation Design—a European Perspective

Time to change the paradigm of children’s medicines from liquid formulations to flexible solid oral dosage forms

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