Application of laminar jet break-up to the preparation of monodisperse microparticulate drug delivery systems
Studies were conducted to investigate the feasibility of using natural laminar jet break-up for the preparation of oil-in-water dispersions for use as templates for the fabrication of monodisperse biodegradable microparticles of controllable sizes suitable for drug delivery. Poly (ε-caprolactone) was used and dissolved in dichloromethane and jetted into a continuous aqueous phase containing a surfactant using a syringe pump.The system was subsequently stirred to facilitate solvent removal leading to polymer precipitation and microparticle formation. Resulting microparticles were characterized by optical microscopy and low angle laser light scattering. The effect of orifice diameter, flow rate within the laminar jet region, and polymer and surfactant concentrations, on the size and polydispersity of the microparticles was investigated. Particles having a narrow size distributions (polydispersity index below 0.35) were produced throughout the laminar jet region under the conditions studied with limitations only on the viscosity of the continuous phase. Particle size and polydisperisty was observed to decrease as the flow rate increased approaching the maximum jet length. However, this effect was less pronounced with smaller diameter orifices. Particle size of the microspheres was dependent on both the orifice size and polymer concentration. For the smallest orifice diameter studied and at a polymer concentration of 1%, the resulting microspheres had a mean diameter larger than that of the orifice while for other orifice diameters (125 - 250 micron), microspheres had mean diameters smaller than that of the orifice. In all cases, the mean diameter of the microsphere was within 30% of the orifice diameter. As expected, particle diameter increased with polymer concentration. These studies demonstrate that microparticles with a narrow size distribution can be prepared from oil-in-water dispersions produced by laminar jet break-up. Further, the size of the resulting microparticles can be controlled and manipulated by varying the orifice size and polymer concentration. Polyester microparticles having a size between 50 and 300 microns suitable for drug delivery can thus be prepared by this method.