Medicine’s a bitter pill to swallow

One of the most exasperating and helpless feelings as a parent is when your child is ill but blatantly refuses to take the medicine that you know will help make them better.

If your child is quite sick, he or she may be particularly irritable, nauseous and finicky, so getting co-operation can be even more of a challenge. Children with chronic conditions can pose additional problems, because taking regular medication becomes a dreaded occurrence and subsequently a source of frustration and anxiety for both. Often the child will protest that it tastes disgusting, and while we sniff it and reassure them that it tastes fine, children do actually perceive taste differently from adults.

Children’s rejection of unpalatable medications is a complex product of maturing sensory systems, genetic variation, experiences and culture.

The perception of taste is different, not only between adults and children, but probably between healthy and sick children also.

Infancy and childhood is a period of rapid growth and development.

The various organs, systems and enzymes that process drugs in the body generally develop gradually but at different rates.

Children cannot be considered as small adults and their bodies do not process all drugs in the same way as adults so the results of clinical studies carried out in the adult population cannot be directly extrapolated to children.

Rapid growth rates, high physical activity levels and changing metabolic profiles during growth compound the difficulty of developing paediatric medicines.

The magnitude of doses required can vary up to 100-fold and the ability to cope with different dosage forms also will vary considerably through childhood.

For example, it is generally extolled that school-age children can swallow a tablet but this is complicated by the size of the tablet, the general health of the child and if a medication is to be taken regularly, the taste of alternatives will often hasten acceptance.

Most medicines have been tested for safe and effective use in adults and there are comparatively few which are specifically licensed for the treatment of children.

In such cases, products are often unavailable in formulations suitable for paediatric administration. The outcome in practice is the preparation and administration of unlicensed medicines, often involving manipulation of adult dosage forms, such as crushing tablets and adding to a thickened liquid.

In both licensed and unlicensed scenarios, whenever administration requires tasting the drug, such as oral liquid formulations, palatability or taste becomes a critical factor in driving patient compliance, prescribing practices, the perceived quality of the drug product, and ultimately its success.

Recent legislation has been put in place in Europe to address unresolved issues relating to children’s needs for medicines but this will mainly apply to applications for new drugs. Medicines contain both the drug substance and additives called excipients.

These additives are required because most medicines could not be manufactured, stored or administered without additional ingredients to ensure efficacy, manufacturability or preservation against contamination. Most drugs have a bitter, unagreeable taste and the ability to mask unpleasant tastes with sweeteners and flavours is of crucial importance in ensuring that the medicine can be tolerated.

Thus excipients such as sweetening agents and flavours are added to mask the foul taste of the drug and help compliance, especially in paediatric formulations.

It is often essential to add a separate flavouring agent to supplement and compliment the sweetening agent and there are flavour groups for different taste types, geographical areas and target disease preferences.

For example, citrus or raspberry are best to mask a sour taste but a bitter taste is best masked with liquorice, coffee, mint or grapefruit — unfamiliar and unpopular flavours for children.

Trying to persuade an ill child to swallow the unfamiliar Grape Splash, or Bubble Gum Yum-flavoured Tylenol (the most common paracetamol children’s brand in the US) is therefore a challenge.

There is a drive to improve palatability by imparting a pleasant flavour and mouthfeel while maintaining an effective, stable dosage form.

This is a significant challenge and there is the added ethical complication: should the medicine actually taste nice? The more pleasurable the taste, the more opportunity for abuse or accidental overdosing, therefore the aim is for somewhere between not being attractive, and not feeling unpleasant.

The addition of sweeteners and flavours to medicines is a balancing act between minimizing additives while formulating a product to enable the active dose to be given accurately and safely.

Mary Poppins may well have the right formula, some sugar and a healthy dose of distraction, singing and story-telling will help the medicine go down.




BARBARA CONWAY is Professor of Pharmaceutics at the School of Applied Sciences, University of Huddersfield.