(184z) Spray Dryer Design for Robust Manufacturing of Amorphous Solid Dispersions

An established enabling technique for enhancing the bioavailability of poorly soluble drugs are ASDs (amorphous solid dispersions), in which the drug molecule is amorphously embedded in a suitable polymer matrix. Spray drying is one of the major techniques for manufacturing ASDs with high melting drugs. The development of an appropriate and robust spray-drying process is challenging as many different variables such as spray drying process parameters or solvents must be selected carefully and tailored to individual needs of the polymer and API. The selected solvent must dissolve enough drug and polymer to generate the spray dryer feed solution. Solvent mixtures can help dissolving cellulose-based polymers such as HPMCAS which are not soluble in single solvents. These solvent mixtures tend reveal different evaporation velocities due to their differing volatilities and boiling points and might thus unevenly evaporate during the droplets’ drying process, leading to a temporary accumulation of one of the solvents. Additionally, the solvent can induce unwanted and hardly detectable amorphous phase separation in the particles during the drying progress, even at the extreme evaporation rates within a spray dryer. The finally obtained spray-dried material always contains residual solvent which usually requires secondary solvent removal. The presentation will highlight the revolutionary potential of using in-silico predictions to address the above-mentioned challenges, from solvent/ solvent mixture screening to predicting the accumulation risk and residual solvent content. This approach using the thermodynamic model PC-SAFT allows predicting scale-up behavior, process design spaces and perform material-property specific sensitivity optimization of process parameters. It requires little experimental training data sets that are typically available at early stages of formulation development. The formulator gains fundamental understanding about the intermolecular interactions within a formulation from a computational in-silico perspective. Development budgets are spent more economically by substituting intensive and misleading trial-and-error screenings or intensive design of experiment studies by this in-silico technique.