(203c) Direct Comparison Between Batch Bulk Mixing and Continuous Millifluidics in the Synthesis of Amorphous Drug Nanoparticles

Amorphous drug nanoparticles in the form of drug-polysaccharide nanoparticle complex (or drug nanoplex) had emerged as an ideal supersaturating delivery system of poorly-soluble drugs attributed to its many attractive characteristics. Herein we presented for the first time direct comparison between two nanoplex synthesis platforms, i.e. millifluidics and bulk mixing, representing continuous and batch production modes, respectively. They were compared by the resultant nanoplex’s (1) physical characteristics (size, zeta potential, payload), (2) preparation efficiency, (3) storage stability, (4) dissolution rate/supersaturation generation, and (5) production consistency. For this purpose, the effects of key variables in drug-polysaccharide complexation (pH, charge ratio) were investigated in both platforms. Perphenazine and dextran sulfate were used as the drug and polysaccharide models, respectively.The results showed that both platforms shared similar dependences on pH and charge ratio with similar optimal preparation conditions. The pH was found as the governing variable through its influence on size and zeta potential, while the other variables (e.g. charge ratio, millifluidics’ residence time, tube diameter) were insignificant. The other aspects of nanoplex were minimally affected by the process variables. Nanoplexes having mostly similar characteristics were produced by both platforms, except for payload and supersaturation generation. Nevertheless, millifluidics was favored owed to its superior production consistency and well-demonstrated scalability.