Advancing Cardiovascular Pharmacotherapy in Children: Development of Age-appropriate Formulations Adaptable for Point-of-care Manufacturing by 3D Printing

About the Project

Cardiovascular diseases (CVDs) in children, such as heart failure, hypertension, and arrhythmias, require chronic treatment with drugs having potentially complicated physicochemical properties. Moreover, nearly all the medications are used "off-label" in paediatric populations due to the lack of age-appropriate commercial formulations [1-3]. Therefore, the common practice by pharmacists currently involves manipulating adult tablets/dosage forms (e.g., crushing, splitting) or preparing extemporaneous liquid suspensions to achieve the required paediatric doses. These improvised methods lead to dose inaccuracy, drug instability, and exposure to potentially toxic excipients to the children [2-4]. Additionally, many cardiovascular drugs are intensely bitter, driving poor adherence and treatment failure [2, 5]. Pharmaceutical 3D printing enables automated on-demand compounding of medicines with the ability to create personalised and customizable dosage forms and sufficiently mark unpleasant tastes of medicines, making them more appropriate for administration in children [2,3]. Moreover, countries such as the United Kingdom began to recognise pharmaceutical additive manufacturing as a promising enabling technology for point-of-care production of personalised medicines at the bedside to enhance patient treatment outcomes [6].

Project aim

This PhD project will develop child-friendly oral dosage forms using pharmaceutical 3D printing with clinically relevant model drugs. Critically, this project will explore the development of single-dose and/or fixed-dose combinations (FDCs) with a roadmap toward clinical implementation at the point of care.

Research Objectives

1. Pre-formulation and early Formulation development: evaluate suitable APIs/excipients and develop printable pharma-inks containing paediatric-relevant doses, including FDCs using biocompatible polymers.
2. Taste masking: Design effective task masking strategies and evaluation of the same using validated models such as electronic tongue technology and/or human volunteers.
3. 3D printing optimisation: Determine optimal 3D printing technology and parameters to achieve the desired product quality profiles.
4. Characterisation and stability: Assess printlets for solid-state, drug content, hardness, disintegration, dissolution, and stability under accelerated conditions and simulated hospital in-use conditions.
5. Clinical translation framework: Develop a quality-by-design (QbD) framework for point-of-care manufacturing and propose a clinical study protocol for acceptability testing in paediatric clinical settings.