Development of Paediatric Medicines-Paediatric Dosage Forms
3. Paediatric Dosage Forms:
The paediatric population is a heterogeneous group ranging from newborns to adolescents with wide physical and developmental differences regarding pharmacokinetics and pharmacodynamics. Organ maturation, metabolic capacity, skin maturation and other factors may change with age, especially in
early infancy (2). The age groups identified by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) (3) have been derived mainly from physiological and pharmacokinetic differences from birth to adulthood:
■ Preterm newborn infants
■ Term newborn infants (0–27 days)
■ Infants and toddlers (28 days–23 months)
■ Children (2–11 years)
■ Adolescents (12 to 16–18 years (dependent on region)).
It is a challenge to find one formulation appropriate for all age groups. The aim should be to safely cover as wide an age range as possible with a single formulation. The guiding principle for selecting paediatric dosage forms should be – as for adults – the balance of risks and benefits taking into account the specific needs of this vulnerable population (4).
During the development of pharmaceutical products, the assessment of individual risks related to specific products and starting materials, and the recognition of hazards at specific stages of production or distribution, will enable further enhancement of the usual quality assurance mechanisms, such as implementation of Good Manufacturing Practices (GMP), by increasing the effectiveness of the activities of all parties involved, within the limits of the available resources. Manufacturers who have chosen a more systematic approach to product development would follow the stages of development within the broader context of quality assurance principles, including the use of quality risk management and pharmaceutical quality systems (4, 5).
Current use of medicines for the paediatric population reflects the full range of dosage forms and routes of administration used for adult medicines. Common routes of administration in paediatric patients include oral, parenteral, dermal, pulmonary, nasal, rectal and ocular. There is, however, limited information on the acceptability of different paediatric dosage forms in relation to age and therapeutic needs and on the safety of excipients in relation to the development of the child. A European Medicines Agency (EMA) reflection paper on paediatric formulations (6) provides background information on these issues. Reviews by Ernest et al. (7) and Krause and Breitkreutz (8) discuss the needs and challenges in developing paediatric medicines.
The desirable features of high-quality paediatric medicines common to all dosage forms are outlined below. Further information on specific dosage forms is given in the following sections.
Development of Paediatric Medicines: points to consider in formulation,
(Annex 5, WHO Technical Report Series 970, 2012)
