The formation of plasmid DNA loaded pharmaceutical powders using supercritical fluid technology

The invention of novel drugs based on biological macromolecules requires th e development of specialized formulation methods. Supercritical fluid techn ology offers the possibility to produce dry powder formulations suitable fo r inhalation or needle-free injection. In this article we describe the firs t application of a process involving supercritical carbon dioxide for the p roduction of plasmid DNA-loaded particles. The technique of solution enhanc ed dispersion by supercritical fluids (SEDS) is used to coformulate the 6.9 kb plasmid pSV beta with mannitol as excipient. After initial experiments showed a high degradation of the plasmid during powder formation, a systema tic investigation of the process revealed pH effects to be crucial for the recovery of intact DNA. The application of high-buffer concentration led to an increase of the recovered supercoiled proportion from 7% to 80%. (C) 20 01 John Wiley & Sons, Inc.