Accelerating paediatric formulation development through smart

design and predictive science (A TSB sponsored project)

Marcel de Matas1 Richard Storey1,2, Nikoletta Fotaki3, Peter Timmins4, John Jones4, Hannah Batchelor5, Andrew Parker6,
7
7
8
9
9
10
11
Catherine Tuleu , Abeer Ahmed , Terry Ernest , Alastair Coupe , Joanne Bennett , Afzal Mohammed , Anita Jackson
1Product

Development, AstraZeneca Pharmaceuticals, Macclesfield, UK. 2Academy of Pharmaceutical Sciences, Leicester, UK. 3Department of Pharmacy, University of Bath, UK. 4Drug Product Design and Technology, Bristol Myers Squibb,
Moreton, UK. 5 Pharmacy, Pharmacology and Therapeutics, University of Birmingham, UK. 6 Molecular Profiles, Nottingham, UK. 7Centre for Paediatric Pharmacy Research, UCL School of Pharmacy, London, UK. 8Product Development,
GlaxoSmithKline, Ware, UK. 9Pharmaceutical R&D, Pfizer, Sandwich, UK. 10Pharmacy, Aston University, Birmingham, UK. 11

Conclusion

Results and discussion

Introduction
Paediatric medicinal products are more

Data sets that compare taste assessment techniques across a range of

Through the work of this consortium,

complex than their adult counterparts owing

model drugs with and without taste modification will guide selection of

we hope to achieve a step-change in

to differences in maturity, physiology and

best tools for deployment in early formulation development. PBPK tools

speed, cost and quality for paediatric

anatomy across the paediatric age range.

will be used to explore the potential impact of taste modification

formulations in development whilst

Flexible dosing, is often required, based on

technology on drug exposure in children. Project activities will also

ensuring a greater probability of

age or weight bands, whilst dosage forms,

include interfacing with patient groups to evaluate and verify patient

regulatory and technical success in an

which provide patient acceptability 2 and

needs and establish key design attributes for optimal paediatric

increasingly challenging environment.

convenience for the carer-giver, but which

formulations (Figure 3). Data will also be captured to support tool

We believe that creation of an industry

do not inhibit drug exposure are essential.

validation in these studies.

standard framework for product

development comprising the latest

At present, industry approaches to

tools for assessing product

paediatric product development are patchy

performance will deliver these aims,

and sub-optimal. No standardised

whilst facilitating the rapid

techniques exist to assess product quality,

development of robust, safe and

which results in excessive iteration and

effective paediatric medicines.

poor productivity in formulation

development. In this regard, it is essential

References

that industry has a better handle on patient

needs and uses this to inform product
design. Areas for which insight is required

1. M. Strohlin Benedetti, R. Whomsley

and for which better methods of

and E.L. Baltes. Differences in ADME of

assessment must be established include

xenobiotics between paediatric and adult

Figure 1. Six workstreams covering the analytical, in-vitro, invivo and in silico techniques to predict the acceptability,
palatability and absorption characteristics of paediatric
medicines

patient acceptability, palatability evaluation

and approaches for predicting exposure in
children. This project, sponsored by the

populations, Expert Opinion on Drug

Metabolism and Toxicology. 1(3) (2005)
447-471.
2.

Technology Strategy Board (TSB), brings

Animal

together experts in paediatric formulation

S.P.

Bryson.

Patient-centred

administration of friendly medicines for

Electrochemical

Electrophysiological

children An evaluation of childrens

development from across the UK, to

Cell based

develop an industry standard framework for

Human

preferences

and

how

medication

adherence.

they

impact

Segment

paediatric product development.

Technology

Journal of Pharmaceutics. 469(2) (2014)

Review existing landscape

and data

Materials and Methods

International

257-259.

Select and test model drugs

Preliminary validation of tools

The consortium has defined six work

Acknowledgements

Innovative technologies for taste assessment

Integrated into paediatric product development framework

streams (Figure 1) which aim to yield the

set of standardised tools and techniques

Figure 2. Proposed approach to establishment of standard suite

of tools for taste assessment

We would like to acknowledge the

Technology Strategy Board and the

to better assess acceptability,

palatability and drug absorption in

Formulation

Taste

Swallowable size Swallowable

(solid)
size (liquid =
volume)

children. There is an also an intention to

Texture
(grittiness)

Viscosity

Time held in
mouth

GSK, BMS, Pfizer and Molecular

Profiles) for funding this project.

use these tools to identify potential

technologies for improving drug
administration. A range of techniques for
taste assessment, including cell based
approaches and electrochemical

Oral Liquid

strategies will be investigated and

Conventional
tablet

Dispersible
tablet

methods (see Figure 2) will be critically

evaluated. Taste modifying formulation

Orally retained
tablet

assessed using the identified palatability

assessment tools. The effect of
palatability modifying formulation
technology on drug pharmacokinetics in
children will be predicted using
physiologically-based pharmacokinetic
modelling (PBPK) alongside biorelevant
dissolution testing.

contributing companies (AstraZeneca,

Figure 3. Examples of the types of attributes which will be explored

in patient centred acceptability studies
The consortium aims to engage with health agencies and the wider
pharmaceutical sciences community to create line of sight to longer
term implementation of these tools as an industry standard for
developing paediatric formulations.