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.
Subject(s)
Acyclovir/analogs & derivatives , Antiviral Agents/administration & dosage , Electronic Nose , Taste , Valine/analogs & derivatives , Acyclovir/administration & dosage , Acyclovir/adverse effects , Acyclovir/chemistry , Administration, Oral , Age Factors , Antiviral Agents/adverse effects , Antiviral Agents/chemistry , Child , Child, Preschool , Cross-Over Studies , Drug Compounding , Humans , Netherlands , Patient Satisfaction , Perceptual Masking , Pharmaceutical Solutions , Tablets , Taste Perception , Valacyclovir , Valine/administration & dosage , Valine/adverse effects , Valine/chemistryABSTRACT
The taste of pharmaceuticals strongly affects the compliance of patients. This study investigated the applicability of the electronic tongue and rodent brief-access taste aversion (BATA) model for the bitter compound praziquantel (PZQ) and taste masked liquid formulations for PZQ. In a comparative study maltodextrin (MD) Kleptose® linecaps 17 was selected as an alternative taste masking agent to two cyclodextrins; hydroxypropyl-beta-cyclodextrin (HP-ß-CD) and sulfobutyl ether-beta-cyclodextrin (SBE-ß-CD). A phase solubility study showed the highest affinity and solubilization capabilities for SBE-ß-CD over HP-ß-CD and MD, suggesting the highest taste masking ability for SBE-ß-CD. No reliable results were achieved for PZQ with the Insent electronic tongue. Thus this system was not used for further evaluation of solutions with MD and CDs to confirm the results of the solubility study. In contrast the BATA model demonstrated conclusive responses for the aversiveness of PZQ. The concentration of PZQ inhibiting 50% of water lick numbers (called IC50 value) was 0.06mg/ml. In contrast to the phase solubility study, the MD enabled an equal taste masking effect in vivo in comparison to both CDs. Moreover HP-ß-CD showed superior taste masking capabilities for PZQ compared to SBE-ß-CD as the SBE-ß-CD itself was less acceptable for the rodents than HP-ß-CD. In conclusion, the BATA model was identified as a more efficient taste assessment tool for the pure PZQ and liquid formulations in contrast to the electronic tongue and the phase solubility study.
