Taste Masking, Solubility Enhancers
5.7 Taste Masking:
Taste masking in medicines for oral use or for use in the mouth is often needed to improve palatability of the medicine. Children have a well-developed sensory system for detecting tastes, smells and chemical irritants. They are able to recognize sweetness and saltiness from an early stage and are also able to recognize a sweet taste in oral liquids and the degree of sweetness (28). Children seem to prefer sweeter tastes than adults do. The unpleasant taste of an API, e.g. bitterness or a metallic taste, is, therefore, often masked in an oral liquid by the use of sweetening agents and flavours. Additional use of colouring agents that match the flavour is discouraged (see section 4.4) unless this is necessary to
disguise an unpleasant colour related to the API. Some successful approaches to taste masking are discussed by Ernest et al. (7).
A child’s preference for particular flavours is determined by individual experiences and culture. The target for taste masking need not necessarily be good-tasting medicines; it should simply be a taste that is acceptable in as many countries as possible taking into account cultural differences.
An example of a “qualitative evaluation of the taste by a taste panel” for zinc formulations can be found in the United Nations Children’s Fund (UNICEF)/ WHO publication on production of zinc formulations (29, 30).
Consideration should be given to the items listed in sections 4.3 and 4.6. Taste masking for orodispersible tablets and chewable tablets is in principle similar to taste masking for oral liquids. Non-cariogenic sweeteners and flavours are preferred.
5.8 Solubility Enhancers:
The aqueous solubility of the API may limit the concentration achievable in formulated solutions and, hence, the desirable dose volume. In many cases an acceptable solution requires solubility enhancing methods, e.g. use of non-ionic surfactants and of co-solvents such as glycerol, liquid macrogols and ethanol. If solubility enhancers are to be used, consideration should be given to the safety of both the agent and the formulation, for example, the risk of irritation and damage of intestinal tissues in neonates caused by hyperosmolality or other local toxicity. Risks associated with the use of solubility enhancers are higher when they are included in parenteral preparations than when used in oral preparations.
Ethanol, especially in large amounts, should not be administered to children (aged 0–17 years) through FPPs without a clear demonstration of benefit. Although it is recognized that ethanol may not always be eliminated from FPPs, and replacements may raise other issues, the smallest possible amount should be
used. When ethanol is used, adequate development data demonstrating that the lowest possible concentration of ethanol is used should be established.
Children, especially under the age of 6 years, are more vulnerable to the effects of ethanol. Adverse effects on the central nervous system are already evident at blood ethanol concentrations of 10 mg/100 ml in children. Higher peak ethanol blood concentrations are also observed in children than in adults
for a similar intake. Chronic exposure to ethanol (> 1 week), even to small doses, through FPPs is, in principle, contraindicated in children aged less than 6 years and should be limited to 2 weeks in children aged over 6 years, if a positive risk– benefit balance is not demonstrated. Toxic effects on brain maturation in young children are highly probable and also supported by non-clinical data. Additionally,
chronic exposure has been shown to be linked to ethanol dependence in adults and adolescents.
Development of Paediatric Medicines: points to consider in formulation,
(Annex 5, WHO Technical Report Series 970, 2012)
