(T1230-05-25) How are Medicines Administered to Pre-school Children? Current Status of a Global Survey on the Use of Dosing Vehicles

Purpose: Children are a challenging patient group when it comes to the administration of oral dosage forms. To improve acceptance, it is common practice, especially in young children, to co-administer the dosage forms with small amounts of soft foods and liquids, so-called dosing vehicles [1]. A dosage vehicle is considered suitable for drug administration if it does not significantly affect the stability or performance of the drug. In the package inserts of oral medicinal products, one often finds a recurring selection of vehicles that have been shown to be suitable for this type of administration of the product in question. Many of these vehicles are also found on the list of commonly used dosing vehicles in the corresponding FDA guidance [2]. But do these recommendations correspond to the vehicles actually used? To determine how oral medicines are administered to children of different ages in everyday life, we designed an online questionnaire for global use. To date, the questionnaire has been completed 619 times, with the majority of responses (275 responses, ~44%) so far relating to pre-school children. We would like to take this opportunity to present the status of the data collected so far for this age group.

Methods: The survey is conducted online and anonymously via soscisurvey.co.uk and surveymonkey.com. The questionnaire is available in 19 languages and includes ten questions on the active ingredient, dosage form, type and amount of co-administered vehicle, and the age of the child. Since it may be important to know who is administering the medicine and whether there are country-specific differences, this information is also collected. Mentioning several active ingredients and vehicles is possible.

Results: The survey results available so far are from 32 countries, with the number of responses from each country varying. In 209 of the 275 cases (76%), the dosage form in question was administered with a vehicle. Figure 1a shows that the oral dosage forms administered with a vehicle are often tablets or granules/powders, in addition to liquid dosage forms. In contrast, the majority of medicines administered without vehicles are, as expected, liquid medicines. The FDA guidance lists 27 dosage vehicles [2]. The survey result for preschool children, however, included 37 different vehicles, which do not include all vehicles listed in the FDA Guidance. Figure 1b shows the ten most frequently mentioned vehicles. By far the most commonly administered drugs were paracetamol (24%) and ibuprofen (17%). Overall, however, the 10 most frequently mentioned drugs represented a very heterogeneous mixture of weakly acidic and neutral drugs that can be classified into BCS classes I, II and III. Even though the adult BCS system cannot be transferred 1:1 to children, this indicates that the choice of dosing vehicle may have a considerable impact on in vivo performance, especially for products containing poorly soluble drugs.

Conclusion: The analysis of the survey results for pre-school children indicates very clearly that in daily life paediatric medicines are administered with a variety of different dosing vehicles, which are not necessarily limited to those mentioned in the relevant package leaflets or FDA guidance. Even liquid oral dosage forms are often administered together with a dosing vehicle. The evaluation also shows that the administered active ingredients differ considerably in their properties, which is why the different dosage vehicles can have distinct influences on their stability and in vivo performance. Therefore, it is very important to investigate this route of administration in more detail.

References: 1. Freerks, L. et al. Vehicles for Drug Administration to Children: Results and Learnings from an In-Depth Screening of FDA-Recommended Liquids and Soft Foods for Product Quality Assessment. Pharm Res 39:497–509 (2022)
2. FDA. Use of Liquids and/or Soft Foods as Vehicles for Drug Administration: General Considerations for Selection and In Vitro Methods for Product Quality Assessments: Guidance for Industry (2018)


Figure 1: Survey results for pre-school children: a) percentage of dosage forms administered with (left) and without (right) dosing vehicles; b) the ten most frequently dosing vehicles sorted by frequency of occurrence