Introduction: The selection and design of dosage form for the paediatric population is a real challenge. Part of that challenge is to deal with the diversity of the patient population (new born to adolescent) (CPMP, 2001) leading to specific patient compliance and acceptability. The choice of an age-appropriate formulation for children aged from 1 to 6 years old requires one to consider the ease of use of the formulation as well as the acceptability which will be mainly driven by palatability. Developing an oral suspension or solution is often preferred as easy to administer but not always possible. In that case, multiparticulate dosage forms (e.g. beads, granules and mini tablets) are encouraged (EMEA, 2006). This work presents a patient focused design of an age-appropriate formulation for an AstraZeneca compound.
Methods: A patient survey, elaborated by AstraZeneca team, was run by Trustech (external consultancy company). The aim was to understand the needs of the patient, parent, caregiver, and clinical team in order to guide the formulation design. The following topics were included in the survey: challenges faced by the child when taking medicines, preferred dosage form, feedbacks on ease of administration. The survey was proposed as a questionnaire sent by postal and/or a face-to-face interview to patient (up to 18 years old), parents and caregivers. 77 responses were collected (44 complete, 33 partially complete). The outcome of the survey was used to define the quality target product profile of the age-appropriate formulation. Prototypes were manufactured: minitablets by direct compression, extrudates by hot melt extrusion and lipid multiparticulates (LMP) by melt spray congealing. Several categories of excipient including filler, lubricant, glidant, disintegrant, water-soluble polymers, plasticizers, lipidic excipient and surfactant were used. Prototypes were evaluated for appearance (by visual inspection and scanning electron microscopy), manufacturability (assessed through critical process parameters) and dissolution performance at pH 6.5 (complete release targeted at 45 min).
Result: Answers were collected for children aged from 1 to 6 years old (21%), 6 to 18 years old (48%) and adult patients remembering childhood experience with medicines (31%). One of the outcome of the survey is summarised in Fig. 1. It shows the level of comfort for different methods of administration/dosage forms, with/without instructions and/or demonstration (1 being the preferred option and 8 the not preferred option).