Scale-up of Polyanhydride Particle Synthesis Methods and Their Effect On Drug Release Kinetics

Polyanhydrides are biodegradable materials which have been shown to provide sustained delivery of their encapsulated payloads. Copolymers based upon sebacic acid (SA), 1,6-bis-(p-carboxyphenoxy)hexane (CPH), and 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaocatane (CPTEG) have previously been synthesized into therapeutic loaded particles through solvent precipitation in our lab. Techniques have been established for the production of polyanhydride particles that are polydisperse on both the micron and nano scale. However, the solvent precipitation method is a batch operation which is not easily scalable.  Therefore, in this work we evaluate the synthesis of polyanhydride particles through solvent evaporation via spray drying, a more easily scalable process. The operating parameters of the spray dryer were optimized with respect to particle yield. Model drugs were encapsulated into the polyanhydride particles to determine encapsulation efficiency and for studies on release kinetics. The resulting polymer particles were also compared to the particles synthesized through a solvent precipitation method for physical particle characteristics (size, surface characteristics, shape and porosity). From these results we show that the method of particle synthesis plays an important role in the performance of drug loaded polyanhydride particles.