Oral formulations for paediatrics: palatability studies

Palatability is one of the main (but not exclusive) pharmaceutical attribute of dosage forms which affect patient’s acceptability of an oral medicinal product and it is crucial for compliance to their treatment. The non-acceptance of a medicine due to the bad taste can have detrimental consequences on the treatment outcome if the medicine is partially or not taken, leading to suboptimal therapeutic effect to no effect at all.

Palatability is defined as the overall appreciation of an (often oral) medicine by organoleptic properties such as vision (appearance), smell, taste, aftertaste and mouth feel (e.g. texture, cooling, heating, trigeminal response), and possibly also sound (auditory clues). It is determined by the characteristics of the active substance (and excipients) and many have aversive taste characteristics. Palatability is also relevant for other routes of administration e.g. buccal, nasal, inhalation use, and whenever the product may contact the taste receptors indirectly e.g. by deposition in the throat, post nasal run off, etc.

The development of paediatric medicines can be challenging since this is a diverse patient population with specific needs. For example, children have different taste preferences. Acceptable palatability of oral paediatric medicinal products is of great importance and this has been recognised by regulatory authorities and so is becoming a key aspect of paediatric pharmaceutical development studies.

As a general rule, acceptability aspects should be embedded in the development program and evaluated, (preferably) during the clinical study with patients from target age group(s). Usually, in vivo sensory analysis (human panels) are used to assess the taste of medicines: volunteers rate the quality and the intensity of test stimuli based on scales. The “swirl and spit” method is the most common one, however knowledge is still fragmented and an internationally harmonized method has not yet been developed. Design of studies requires careful considerations.

Finally as palatability studies with human taste panels are usually carried out at the latter stages of formulation development if at all, there is a great need to develop a means to assess the taste of APIs and formulations at early stages of drug development so that taste aversive compounds are highlighted early, formulations are optimised and taste masking approaches are put in place.

References

• Ranmal S, Tuleu C. Demonstrating evidence of acceptability: the "catch-22" of pediatric formulation development. Clin Pharmacol Ther. 2013 Nov;94(5):582-4.

• Guideline on pharmaceutical development of medicines for paediatric use (Doc. Ref.: EMA/CHMP/QWP/805880/2012 Rev. 2)

• Cram A, Breitkreutz J, Desset-Brèthes S, Nunn T, Tuleu C; Challenges of developing palatable oral paediatric formulations Int J Pharm. 2009 Jan 5;365(1-2):1-3.

• Walsh J, Cram A, Woertz K, Breitkreutz J, Winzenburg G, Turner R, Tuleu C Playing hide and seek with poorly tasting paediatric medicines: do not forget the excipients. Adv Drug Deliv Rev. 2014 Jun;73:14-33.

• Davies EH, Tuleu C. Medicines for children: a matter of taste. J Pediatr. 2008 Nov;153(5):599-604, 604.e1-2.