WHO TRS (Technical Report Series) 970, 2012 Annex 5


WHO TRS (Technical Report Series) 970, 2012 Annex 5

Development of paediatric medicines: points to consider in formulation

1. Introduction

Safe and effective pharmacotherapy for paediatric patients requires the timely development of medicines and information on their proper use appropriate to the age, physiological condition and body size of the child. Formulations developed specifically for children are often needed. The use of unlicensed and off-label medicines for treating children is widespread. Their effects on children have not been properly studied, age-appropriate formulations are generally not available, and the medicines are not licensed for use in children. 

Pharmacists, parents or caregivers are often faced with the need to manipulate an adult medicine in a way that is not described in the Summary of product characteristics. This manipulation can be simple, e.g. breaking tablets that do not have a score line with a tablet splitter, or complex, e.g. using tablets as a source for an active pharmaceutical ingredient (API) to prepare a suspension. Pharmacists may also be faced with the need to compound a medicine on the basis of the API.

The manipulation process itself can increase the potential for inaccurate dosing and in general can increase the variability of the product. Such handling may be potentially hazardous for the patient as it may affect the stability, bioavailability and accuracy of dosing of a finished pharmaceutical product (FPP), in particular for controlled-release preparations. The use of such medicines may expose children to overdosing and unintended side-effects or to under dosing and a resultant reduction in efficacy. Moreover, excipients that are safe for adults may not necessarily be so for children.

In December 2007 WHO launched its initiative “Make medicines child size” in order to raise awareness of and accelerate action to meet the need for improved availability and access to child-specific medicines. The WHO Model Formulary for children, 2010, provides independent prescriber information on dosage and treatment guidance for medicines based on the WHO Model List of essential medicines for children, first developed in 2007 and reviewed and updated every two years. 

Among actions to support the “Make medicines child size” initiative is the present “Points to consider” document on the formulation of paediatric medicines. The objective is to inform regulatory authorities and manufacturers on issues that require special attention in pharmaceutical formulation. Its focus is on the conditions and needs in developing countries. The guidance does not provide exhaustive information and does not exclude the possibility that other aspects may be relevant to the development of paediatric medicines.

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Table of Contents

1. Introduction 

2. Glossary 

3. Paediatric dosage forms 

3.1 Convenient, reliable administration 

3.2 Acceptability and palatability 

3.3 Minimum dosing frequency 

3.4 End-user needs 

4. Particular dosage forms to be considered 

4.1 Flexible solid dosage forms 

4.2 Oral medicines 

4.3 Medicines for severe conditions 

4.4 Rectal preparations 

5. Formulation design 

5.1 Quality 

5.2 Biopharmaceutics classification system 

5.3 Excipients 

5.4 Colouring agents 

5.5 Antimicrobial preservatives 

5.6 Sweetening agents 

5.7 Taste masking 

5.8 Solubility enhancers 

6. Oral administration 

6.1 Oral liquid preparations 

6.2 Administration through feeding tubes 

6.3 Oral solid dosage forms 

7. Rectal administration 

7.1 Suppositories 

7.2 Rectal liquids (enemas) 

8. Parenteral administration

8.1 Formulation 

8.2 Additional points to consider for parenteral preparations 

9. Dermal and transdermal administration 

9.1 Transdermal patches 

10. Inhalations

11. Packaging and labelling 


WHO TRS (Technical Report Series) 970, 2012 Annex 5:


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