The objective of this project is for the ESR to gain skills and generate data on the nucleation and crystal growth and molecular dynamic modelling of the selected class of APIs during batch and continuous supercritical antisolvent assisted spray drying for the generation of nanosuspensions. Optimal process conditions and excipients will be selected to obtain a specific polymorphic form and crystal size distribution which will be verified experimentally using supercritical fluid antisolvent precipitation approaches. Production and isolation of nanoparticles from supercritical antisolvent assisted spray drying into aqueous nanosuspension will be optimised in a single step. Molecular simulations (Density Functional Theory) on excipient-API interactions will guide in the selection of the optimal excipient to enhance nucleation, promote the formation and stability of a specific polymorphic form, reduce subsequent particle growth and stabilise the desired resultant particle size distribution, which will be verified experimentally. Control over the resultant polymorphic form will be demonstrated and controlled release kinetics of suspension in biorelevant media suitable for target application will be demonstrated. A long acting stable suspension with appropriate release kinetics will be designed. This project will form the basis for a predictive process model. Finally, the developed production method will be verified against the current Janssen top down technologies long acting nanosuspensions.
