Acceptability of placebo multiparticulate formulations in children and adults

Abstract

Patient acceptability is an important consideration in the design of medicines for children. The aim of this study was to investigate acceptability of multiparticulates in healthy children and adults. A randomised, single-blind acceptability testing was performed involving 71 children (4-12 years) and 61 adults (18-37 years). Each participant received three 500 mg samples of microcrystalline cellulose pellets administered on a medicine spoon with water at 5-10 minutes intervals. Acceptability was measured based on voluntary intake of the samples, facial expressions, ratings on hedonic scales and reported willingness to take multiparticulates everyday as a medicine. Multiparticulates were voluntarily swallowed by 92% of children and 100% of adults. However, palatability issues were identified, with emphasis on textural aspects. Grittiness perception received negative ratings on hedonic scales by 60% of children and 51% of adults. Researcher observations revealed that 72% of children and 42% of adults displayed negative facial expressions towards the samples. Children reported their willingness to take multiparticulates as a medicine in 30% of the cases, compared to 74% in adults. This study demonstrates that multiparticulates may be a suitable formulation platform for children and adults, although palatability concerns have been highlighted. Additional work is required to define acceptability criteria and to standardise methodologies.

Figure 1

Ratings of sample attributes in hedonic scales (where 1 represents ‘extremely liked’ and 5 represents ‘extremely disliked’) by population group. This graph shows pooled data from all different samples (4 particle sizes, coated/uncoated). Centre lines show the medians, box limits indicate the 25th and 75th percentiles, notches represent the 95% confidence interval of the median and outliers are denoted by dots; crosses represent sample means and bars indicate 95% confidence intervals of the means.

Figure 2

Ratings of sample attributes in hedonic scales as a function of multiparticulate size and presence of polymeric coating, by population group. Markers represent the combined average rating of grittiness, mouthfeel, taste and sample volume and bars represent the 95% confidence interval.

Figure 3

Proportion of participants reporting willingness to take multiparticulates everyday if it was a medicine.

Figure 4

(A) Volume of water consumed as a function of multiparticulate size, where centre lines show the medians, box limits indicate the 25th and 75th percentiles and outliers are denoted by dots. (B) Proportion of participants that reported they could still feel residual multiparticulates in their mouth after sample intake, as a function of particle size.

Figure 5

Samples of 500 mg of placebo multiparticulates dispersed in approximately 3 ml of spring water on a medicine dosing spoon. The particle size of the multiparticulates varies, from left to right: 200–355, 350–500, 500–710 and 700–1000 μm.