Palatability and acceptability of multiparticulate formulations: adults vs.

children comparison
F. Lopez1, P. Mistry2, H. Batchelor2, J. Bennett3, T. Ernest4, M. Orlu Gul1 and C. Tuleu1
1 University College London, School of Pharmacy, 29-39 Brunswick Square, London, WC1N 1AX, UK
2 University of Birmingham, School of Pharmacy, Institute of Clinical Sciences, Edgbaston, B15 2TT, UK
3 Pfizer Global R & D, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK
4 GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, CM19 5AW, UK

INTRODUCTION RESULTS AND DISCUSSION

Evaluation of palatability and acceptability should be an Overall acceptability of multiparticulates

integral part of the pharmaceutical development of paediatric In the case of children, the sample was refused on 7 out of 213 occasions
medicines. However, there is no standardised methodology and the sample was spat out by the child on 9 instances. In the case of
for palatability and acceptability testing. adults, the sample was never refused nor spat out (out of 183 occasions).
Therefore, the ability to swallow multiparticulates was 92.5% in children and
Multiparticulates, in the form of pellets or beads, offer 100% in adults. However, the self-reported willingness to take the sample
potential benefits over conventional solid and liquid every day was 73.8% in adults and only 29.6% in children (C).
formulations. However, palatability and patient acceptability of
multiparticulate formulations is not well established. C Adults Children

26.2%
AIMS
70.4%
4.2%
100% 92.5%
To develop methodology for palatability and acceptability testing 73.8% 3.3%

29.6%
To evaluate multiparticulate formulations in adults and children

Refused Spat out Swallowed Not willing Willing Refused Spat out Swallowed Not willing Willing
EXPERIMENTAL METHODS to take sample everyday to take sample everyday

Study design: Samples were composed of cellulose pellets of 4 distinct Facial expressions and behaviours
particle sizes available as coated or uncoated versions of each size (A). There were only 9 occasions when children voiced resistance (before or
Participants received three 500 mg samples of placebo multiparticulates on during administration) and 20 occasions when children voiced disgust (post
a medicine spoon with approximately 3 mL of spring water. administration). Such behaviours were not detected for adult participants (D).
Facial expressions suggest some level of discomfort, which was consistently
A
higher in children than adults. It is not possible to determine which are signs
of non-acceptance and which are a result of ingestion of a novel material.

Particle size (m) D Adults Children

200-355 350-500 500-710 700-1000 Children 4-12 years Acceptability in children
N=71, median=7 200-355m 350-500m 500-710m 700-1000m 200-355m 350-500m 500-710m 700-1000m
Coated/Uncoated

Sample 1
100 100

% samples displaying behaviour

% samples displaying behaviour

5-10 min break Facial expressions Negative behaviours Facial expressions Negative behaviours
80 80
Sample 2
5-10 min break 60 60

Sample 3
N=61, median=22 40 40

500 mg sample with 3 ml water Adults 18-37 years Acceptability in adults

20 20

0 0

After each sample intake participants had free access to water to clean their palate. Subject-reported outcomes: effect of formulation factors
There were no trends to suggest that there was an optimum particle size;
Evaluation tool: A combination of researchers observations and subject- although the largest particle size fraction was less favoured by adults this
reported outcomes were used to assess palatability and acceptability of was not the case in children (E). In addition, no significant differences in
multiparticulate formulations by children and adults (B). palatability of coated and uncoated particles were found (data not shown).

B E Adults Children
Researcher observations Subject-reported outcomes
100% 100%
(Before, during and after sample intake)
Number of participants (%)

(Immediately after sample intake)

Number of participants (%)

80%
5 5 80%
Grittiness

4 4
60% 60%
Hedonic scales: grittiness, volume, mouthfeel, taste 60.0 62.5 3 3
% volunteers able to swallow the 40%
40% 54.0 43.1
complete dose of multiparticulates 2 2 39.6 36.4 40.4
20% 20%
4x 20.8 1 1
0% 0%
200-355 m 350-500 m 500-710 m 700-1000 m 200-355 m 350-500 m 500-710 m 700-1000 m

Facial expressions and negative If this was a medicine, would you be willing to take Preference for smaller sizes (p = 0.039) No particle size preference (p = 0.306)
behaviours towards the samples this every day?
100% 100%
Number of participants (%)

Number of participants (%)

Yes No 80% 73.8% 80%

Willingness

87.5
Facial expression Negative behaviours 74.6 74.0
60% 60%
Eyes squeezed/shut Voices resistance (prior) 60.4
Text box for open-ended responses about samples 40% 40%
Brow bulge (frown) Voices disgust (post) 39.3
Nose wrinkle Cries/screams
20% 20% 30.6 31.4
29.6%
17.5
Pursed lips Vomits 0% 0%
200-355 m 350-500 m 500-710 m 700-1000 m 200-355 m 350-500 m 500-710 m 700-1000 m

CONCLUSIONS

The ability to swallow the complete dose of multiparticulates (500 mg) was 92.5% in children and 100% in adults; however, the willingness to take the sample
everyday was only 29.6% and 73.8%, respectively. Adults preferred smaller particles (<700 m) whereas children showed no size preference.
The results of this study highlight methodology barriers to evaluate palatability and acceptability of pharmaceutical formulations. Different methods to measure
acceptability may result in different outcomes. Further studies are needed to develop standardised methodology for palatability and acceptability testing.

ACKNOWLEDGEMENTS

EPSRC grant: EP/I01375X/1