(195a) Enhancement of Particle Collection Efficiency in Electrohydrodynamic Atomization Processes for Pharmaceutical Particle Fabrication

Electrohydrodynamic atomization (EHDA) received considerable research attention recently due to its ability to generate monodispersed droplets and particles for pharmaceutical applications. EHDA can be performed in a shuttle glass chamber by enclosing a nozzle and a ring electrode while connecting both to high-voltage DC power supplies independently for fine-tuning of the electric field around the tip of nozzle. The ring is deployed so that a better control of the EHDA spray could be achieved. Conversely, the ground collecting plate acts as the counter electrode to the nozzle and ring for discharging and collection of the particles. Solution, which is consisted of biodegradable polymer, drug and organic solvent, is pumped out through the nozzle using a programmable syringe pump. Nitrogen (acting as an inert gas) is connected to one end of the chamber while keeping the other end as the gas outlet such that the collection rate of the particles can be adjusted through controlling the pneumatic conveying of the droplets. Particle collection efficiency and residual solvent in the collected particles are two important performance indicators for optimal design on the fabrication systems of pharmaceutical particles. Since the cost for raw materials is a major concern, higher particle collection efficiency is extremely desirable. Moreover, tight control on the concentration of residual solvent in the collected particles after EHDA process is desirable because it eliminates the use of freeze-drying as a mandatory, energy-consuming step towards the final processing of particles.

In the present study, EHDA is employed to produce biodegradable polymeric microparticles in a new generation of shuttle glass chamber. Three major improvements can be found in this new glass chamber. Firstly, the chamber is completely cylindrical without the use of any conical ends. Secondly, the particles are collected inside the vessel at a location far from the spray zone. Thirdly, nitrogen inlet and outlet diameters are scaled up from earlier designs. These modifications markedly influenced both the reverse flow of inert gas and the flight time of the particles inside the chamber. As a result, weaker reverse flow, higher particle collection efficiency and lower amount of residual organic solvent in the collected particles are the main improvements achieved by the above-mentioned modifications.

The effects of different operating parameters including polymer solution flow rate, nitrogen flow rate, nozzle and ring voltage on the particle collection efficiency and residual amount of organic solvent in collected particles are investigated. The Taguchi method is used to optimize the collection condition for systematic investigation on the main parameters affecting the particle collection efficiency. Duration of the process and electrical conductivity of organic solvent are found to be the two other minor factors that can also affect the particle collection efficiency. For all the trials attempted in the study, the residual DCM contents of the particles fabricated are found to be significantly lower than the safety standards (600 ppm) at the end of EHDA process without engaging any additional freeze-drying process. In summary, this study aims to understand the use of EHDA process for polymeric particle fabrication to achieve better collection efficiency and solvent evaporation rate through systematic sensitivity analysis on relevant process parameters.

Key words: Electrohydrodynamic atomization; particle collection; efficiency; Taguchi; microparticle; residual solvent.