- Selection of the drug delivery technology and modelling of the target release profile.
- Examples of initial digital design for osmotic pump ER formulations in early phase clinical studies.
- Enhanced control of film properties and dissolution via comprehensive process modelling and PAT for function coatings.
- Scale-up and optimization of the functional coating process via first principles, empirical, and digital twin simulations from lab to commercial scale.
- Eliminating or minimizing scale-up by use of the small batch or semi-continuous processes for functional coatings.
PK modelling has long been used to generate the target in-vivo release and PK profiles. The drug delivery technology is then selected or matched with the biopharmaceutical objectives and patient medical need. Formulation models have enabled digital design for initial prototype key attributes (e.g., functional coating weight gain) to achieve the target in-vitro dissolution profile. More recently coating models have advanced to guide in scale-up from lab through commercial scale via first principles, empirical models and more comprehensive digital twins coupling the discrete element method (DEM) and computational fluid dynamics (CFD). These models and new process analytical technology (PAT) are helpful to maintain consistent product performance by reducing variability in functional coating amounts or changes in coating morphology with process scale (e.g., batch size) or equipment design. Additionally, there are new, small scale coating equipment designs that can be leveraged to reduce or avoid scale-up altogether.
Alfred Berchielli, Associate Research Fellow, Drug Product Design, Pfizer