| This work presents novel antisolvent processing technique entitled Compressed Antisolvent Precipitation and Photopolymerization (CAPP) useful for forming crosslinked polymer microparticles. In this process, an organic solvent dissolves monomer and polymerization photoinitiators to form a homogeneous solution. Photopolymerization and microparticle formation occur when the homogeneous solution is sprayed into a compressed antisolvent while being simultaneously exposed to initiating light. We investigated the method of particle formation in the CAPP process to explain the repeatable bimodal particle size distribution obtained under a variety of operating conditions. Ternary phase diagrams of antisolvent, monomer, and solvent solutions were constructed and specific spray paths from the resulting ternary phase diagrams were investigated and the significance of crossing the binodal, as well as the importance of where the binodal was crossed, was discovered. In addition, manipulation of injection conditions, varying process residence times, and nucleation rate calculations were explored to further investigate the means of particle formation.; We demonstrate the feasibility of encapsulating therapeutic agents into highly crosslinked polymer particles using the CAPP process. Ion-paired tacrine, erythromycin, erythromycin estolate, and erythromycin ethyl succinate were CAPP processed with poly(ethylene glycol) diacrylate monomers of several molecular weights so that the resulting particles would entrap different sized drugs in networks with varying mesh sizes. In vitro drug release profiles were obtained for all of the various drug-monomer combinations. Diffusion coefficients were estimated by fitting a short time approximation of Fickian release from a sphere of fixed diameter to the release data and were applied to a model of Fickian release from polydisperse spheres, and the results were compared to the in vitro release data. CAPP particle processing was explored in acetone, ethanol, and methanol with respect to reaction kinetics, particle size and morphology, particle double bond conversion, and in vitro drug release.; A multifunctional anhydride monomer was also applied to the CAPP process and ion-paired tacrine was successfully encapsulated in the resulting surface eroding, crosslinked polymer microparticles. Degradation of and release from thin disks of photopolymerized monomer, poly(sebacic anhydride dimethacrylate), gave a kinetic constant for surface erosion, which was applied to predict the release of ion-paired tacrine from the CAPP-processed, degradable particles. |
