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. 2023 Jul 4;15(7):1879.
doi: 10.3390/pharmaceutics15071879.

Responsive Sensory Evaluation to Develop Flexible Taste-Masked Paediatric Primaquine Tablets against Malaria for Low-Resource Settings

Sejal R Ranmal  1 , Marc Lavarde  2 , Elodie Wallon  2 , Samar Issa  2 , Walter R Taylor  3   4 , Julie L A Nguyen Ngoc Pouplin  5 , Catherine Tuleu  1 , Anne-Marie Pensé-Lhéritier  2
Affiliations

Responsive Sensory Evaluation to Develop Flexible Taste-Masked Paediatric Primaquine Tablets against Malaria for Low-Resource Settings

Sejal R Ranmal et al. Pharmaceutics. .

Abstract

Primaquine is an important antimalarial drug for malaria transmission blocking and radical cure, but it is not currently available in child-friendly formulations in appropriate doses. Adult-strength tablets are often crushed and dissolved in water to obtain the required dose, which exposes the drug's bitter taste. As part of the developing paediatric primaquine (DPP) project, this study adopted a responsive sensory pharmaceutics approach by integrating real-time formulation development and pre-clinical taste assessment to develop palatable, flavour-infused primaquine tablets. A design of experiment (DoE) approach was used to screen different taste-masking agents and excipient blends with trained, expert sensory assessors, with quinine hydrochloride as a model bitter tastant. The taste-masking efficacy of selected prototype formulation blends was validated with naïve assessors using the highest 15 mg primaquine dose. The mean bitterness intensity rating, measured on a discrete 11-point scale, was halved from 7.04 for the unflavoured control to 2.74-3.70 for the formulation blends. Sucralose had the biggest impact on bitterness suppression and improving palatability. Two different flavouring systems have been developed, and their acceptability in paediatric patients will be assessed as part of upcoming validation field clinical trials in Africa.

Keywords: acceptability; child; design of experiments; human taste panel; malaria; paediatric formulation; palatability; primaquine; quality target product profile; sensory evaluation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Validation process for the statistical methods.
Figure 2
Figure 2
Results of the end-user survey, including (a) countries where survey respondents were located and (b) frequency of flavours reported by respondents.
Figure 3
Figure 3
(a) Pareto chart of bitterness for the main effect model; and (b) Cube plot with mean of bitterness for the trials of the design.
Figure 4
Figure 4
Boxplots illustrating the bitterness intensity ratings for the flavour blend formulations. Centre lines show the medians, and crosses represent the sample means. Box limits indicate the 25th and 75th percentiles, and whiskers extend 1.5 times the interquartile range.
Figure 5
Figure 5
Boxplots illustrating the bitterness intensity ratings for the optimised formulations. Nemenyi’s post-hoc test classified formulation A into group I and formulations B–G into group II, indicating that all flavour blends were significantly less bitter than the control; however, there were no significant differences between the six different flavour blends. Centre lines show the medians; crosses represent the sample means; and outliers are represented by dots. Box limits indicate the 25th and 75th percentiles, and whiskers extend 1.5 times the interquartile range.
Figure 6
Figure 6
Boxplots illustrating the ratings for the overall sensory experience/sample acceptability captured on the 5-point facial hedonic scale. Centre lines show the medians; crosses represent the sample means; and outliers are represented by dots. Box limits indicate the 25th and 75th percentiles, and whiskers extend 1.5 times the interquartile range.
See this image and copyright information in PMC

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