Evidence of acceptability of oral paediatric medicines: a review

Abstract

Objectives The aim of this review was to map the currently available evidence on acceptability of oral paediatric medicines to aid in the selection of suitable platform formulations for the development of new acceptable paediatric products. Methods This process used a defined search strategy of indexed publications and included methods to assess the quality of the evidence retrieved. Key findings Taste/palatability was the most extensively studied area of paediatric medicine acceptability yet standard methods or criteria that define what is classed as acceptable to children is still to be defined. There have been many reports on the acceptability of medicines to paediatric populations yet major gaps in the acceptability knowledge base exist including the shape and dimensions of tablets, minitablets and capsules swallowed whole in infants and children; size and overall volume of multiparticulates; volume of liquids completely swallowed in infants and children; duration of retention within the oral cavity, size and taste of orodispersible tablets, lozenges and chewable tablets and the number of solid units dosed at each time point. Conclusions The review highlights where further information is required to support knowledge around acceptability of age-appropriate medicines. An algorithm to aid in selection of a formulation that is likely to be acceptable based on the age range to be treated by the medicine is presented as a result of this review. IntroductionThere is much evidence to support the need for age-appropriate medicines to treat paediatric patients. Pharmaceutical products for the paediatric population have a number of considerations that may not apply to adult products. In particular, the acceptability of a product needs to be clearly defined for paediatric populations and this is currently an area of great interest.The importance and incentive to study the acceptability, including palatability, of paediatric formulations was discussed in the reflection paper [1] and endorsed in the latest European Paediatric guideline on pharmaceutical development of formulations for paediatric use.[2] Before this regulatory change, there was no requirement for medicines to be demonstrated to be acceptable to children. Guidance issued by the European Medicines Agency (EMA) in 2013 states that patient acceptability must be an integral part of paediatric formulation development and described in the paediatric investigation plan (PIP).[3] Acceptability has previously been defined as 'an overall ability of the patient and caregiver (defined as "user") to use a medicinal product as intended (or authorised)'.[4] The palatability of paediatric medicines is one of the most important formulation factors in the acceptability of liquid medicines with potential to influence adherence to therapeutic regimens and outcomes.[5] Palatability has been defined as, 'the overall appreciation of a (often oral) medicine by organoleptic properties such as vision (appearance), smell, taste, aftertaste and mouth feel (e.g. texture, cooli...

A systematic review of the use of dosage form manipulation to obtain required doses to inform use of manipulation in paediatric practice

“…Mistry and Batchelor (2016) highlighted the need for 568 support knowledge around the acceptability of age-appropriate medicines and presented anthat tablets larger than 8 mm could be split only once to achieve an approximate half dose for 571 paediatric use. The authors could not recommend that tablets be split more than once due to a 572 lack of weight uniformity of the part tablets after splitting.…”

“…The authors could not recommend that tablets be split more than once due to a 572 lack of weight uniformity of the part tablets after splitting. Both Mistry and Batchelor (2016) and 573 Andersson et al (2016) concluded that more age-appropriate dosage forms, including small 574 tablets, should be available to children. Andersson et al (2016) considered that non-functional 575 score lines should be avoided since both patients and health professionals falsely believed that a 576 score line indicates the possibility of dividing the tablet in two equal parts.…”

“…Mistry and Batchelor (2016) highlighted the need for 568 support knowledge around the acceptability of age-appropriate medicines and presented an 569 algorithm to aid in formulation selection based on age range. Andersson et al (2016) concluded 570 21 that tablets larger than 8 mm could be split only once to achieve an approximate half dose for 571 paediatric use.…”

The Utility of the Artificial Taste Sensor in Evaluating the Bitterness of Drugs: Correlation with Responses of Human TASTE2 Receptors (hTAS2Rs)

“…High correlation coefficients (>0. 7) were observed between the responses of AC0 and hTAS2R14 (0.72) and slight correlation coefficients (0.4<, <0.7) were observed between the responses of AC0 and hTAS2R40 (0.53), between AN0 and hTAS2R10 (0.43), hTAS2R14 (0.42) and hTAS2R44 (0.58), between BT0 and hTAS2R14 (0.46), and between AE1 and hTAS2R8 (0.46) and hTAS2R41 (0.46). Fisher's exact tests were carried out for these correlations.…”

“…[7][8][9] Huge efforts have been devoted by industry and academia in the development of taste-masked pharmaceuticals. 10,11) However, compliance issues, stemming from the bitter taste of active pharmaceutical ingredients, are still common.…”