(14g) Experimental and Model-Based Optimization of a Secondary Drying Process for a Spray Dried Dispersion Product

Spray dried dispersions (SDD) are becoming increasingly common for pharmaceutical small molecule compounds in development due to their ability to enhance bioavailability. Typically, a secondary drying process follows spray drying to remove excess residual solvent in order to meet standards set by the FDA. Compared to secondary drying of crystalline materials, kinetics for drying SDDs are much slower due to their porous internal structure and tendency to retain solvents. To minimize the secondary drying time, we must establish a good understanding of material and processing variables affecting drying performance. We present here a study based on BMS compound A, which is an SDD product with HPMC-AS. Wet SDD products from spray drying of compound A containing about 7% residual acetone were dried using a variety of process equipment and scales. The drying was monitored using a suite of process analytical technology (PAT) tools including analytical balance, Raman spectroscopy and mass spectroscopy under different processing conditions. Material properties relevant to drying performance were measured separately offline. Internal diffusion and external mass transfer assumptions during secondary drying were tested using small scale tray drying and large scale agitated drying experiments, respectively. Important factors that impact drying rate of SDD were identified. Ultimately, a model was developed based on the experimental data and was used to evaluate different drying approaches to evaluate risk and to support scale-up and technology transfer activities.