In vivo and in vitro palatability testing of a new paediatric formulation of valaciclovir

Diane E T Bastiaans, Laura I Immohr, Gertrude G Zeinstra, Riet Strik-Albers, Miriam Pein-Hackelbusch, Michiel van der Flier, Anton F J de Haan, Jaap Jan Boelens, Arjan C Lankester, David M Burger, Adilia Warris, Diane E T Bastiaans, Laura I Immohr, Gertrude G Zeinstra, Riet Strik-Albers, Miriam Pein-Hackelbusch, Michiel van der Flier, Anton F J de Haan, Jaap Jan Boelens, Arjan C Lankester, David M Burger, Adilia Warris

Abstract

Aims: The palatability of a new paediatric formulation of valaciclovir was assessed in children and their parents: non-inferiority of the new paediatric formulation (test formulation) compared to the reference formulation was investigated.

Methods: In vivo palatability testing was performed in a randomized, two-period, multicentre, cross-over study. Children and their parents scored the liking of the new paediatric valaciclovir formulation and the reference formulation on a 100 mm visual analogue scale (VAS). To support formulation development and palatability testing, electronic tongue measurements were applied.

Results: The electronic tongue measurement indicated taste-masking capabilities for three different formulations in the developmental phase. A glycerol-based formulation was further tested and compared to the reference formulation prepared out of crushed and suspended tablets. The mean difference (95% CI) in VAS scores between both formulations, as indicated by the children (n = 20), was 2.4 (-8.5, 13) mm, in favour of the new paediatric valaciclovir formulation. The mean (95% CI) difference in VAS scores indicated by the parents (n = 20) was -0.9 (-12, 9.8) mm.

Conclusion: The palatability of the new paediatric valaciclovir formulation was considered non-inferior to the reference formulation prepared out of crushed tablets. We were able to optimize the study design and number of children to be included in the palatability testing by using electronic tongue measurements.

Keywords: drug development; infectious diseases; paediatrics; pharmacotherapy; quality use of medicines.

© 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Figures

Figure 1
Figure 1
Applied combined 100 mm visual analogue/facial hedonic scale
Figure 2
Figure 2
PCA map for the formulation development of valaciclovir (mean, n = 3, R2 = 0.920, Q2 = 0.508): Val20/50: valaciclovir in water (20 and 50 mg ml−1); A1/2, B1/2 and C1/2: vehicles; Val20/50_A/B/C: valaciclovir in vehicles A, B and C (20 and 50 mg ml−1)
Figure 3
Figure 3
PCA map comparing the test and reference formulation containing valaciclovir in different concentrations (mean, n = 3, R2 = 0.990, Q2 = 0.932): Val20: valaciclovir in water (20 mg ml−1); Test: vehicle of test formulation; Reference: vehicle of reference formulation; Val20/50_test: valaciclovir test formulation (20 and 50 mg ml−1); Val25/50_ref: valaciclovir reference formulation (25 and 50 mg ml−1)
Figure 4
Figure 4
Euclidean distances of the drug formulations compared to either the corresponding vehicle (black) or the corresponding samples of valaciclovir in water (red) (n = 3): Val20/50_test: valaciclovir in vehicle of test formulation (20 and 50 mg ml−1); Val25/50_ref: valaciclovir in vehicles of reference formulation (25 and 50 mg ml−1)

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