Playing hide and seek with poorly tasting paediatric medicines: Do not forget the excipients

Walsh, Jennifer; Cram, Anne; Woertz, Katharina; Breitkreutz, Jörg; Winzenburg, Gesine; Turner, Roy; Tuleu, Catherine

doi:10.1016/j.addr.2014.02.012

Cited by 195 publications

(147 citation statements)

References 87 publications

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“…There has been a notable shift towards the development of solid formulations over liquids, given the 40 limitations with stability, palatability, and costs associated with the latter (Lajoinie et al, 2014, Venables, 2013, Walsh et al, 2014. Rapidly advancing innovative technologies such as (oro-)dispersible, multiparticulate and chewable preparations offer the key advantages of solid dosage forms, together with the flexibility of dosing and ease of ingestion traditionally associated with liquids.…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…For example, the medicine may not be commercially available in the required strength (a 2 mg tablet needs breaking or splitting to administer a 1 mg dose), the medicine may not be available in a dosage form that the child is able to take (babies cannot swallow large tablets), or the medicine may not be available in a dosage form that the child is willing to take (bad taste; adequate taste, but child does not like it; recalcitrance) (Balakrishnan et al, 2007;Balakrishnan et al, 2006;van Riet-Nales et al, 2011;Walsh et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Methods of administering oral formulations and child acceptability

Riet‐Nales

Ferreira

Schobben

et al. 2015

International Journal of Pharmaceutics

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“…Adequate patient acceptability is key to drug efficacy and safety (33,50,54). According to the EMA paediatric guideline, patient acceptability is determined by the characteristics of the drug product and the user.…”

Section: Paediatric Drug Product Design: Patient Acceptabilitymentioning

confidence: 99%

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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Playing hide and seek with poorly tasting paediatric medicines: Do not forget the excipients

Cited by 195 publications

References 87 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

Methods of administering oral formulations and child acceptability

Paediatric Drug Development and Formulation Design—a European Perspective

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