Low-temperature evaporation of continuous pharmaceutical process streams in a bubble column

Abstract

A lab-scale (0.03m di, 0.4m H) bubble column is investigated as a means of achieving low-temperature evaporation of process streams containing dissolved pharmaceutical APIs in batch and continuous modes. A thermodynamic model is developed from first principles which predicts the rate of evaporation of pure solvents, using a dry stream of air bubbles as the driving force for the mass transfer from a liquid to a gas phase. This model is validated experimentally, and it is demonstrated that saturation is achieved almost instantaneously between liquid and the gas, highlighting the efficiency and potential of this method. Maintaining the bubble flow in the homogeneous regime, various rates of solvent evaporation were achieved based on the solvent's characteristic volatility and fixed process variables. All modelling prediction rates of evaporation of pure solvents are within satisfactory errors of experimental measurements (<5% absolute). Batch experiments were performed with solutions of API and a reduction in predicted evaporation rate was observed. Based on experimental results from batch mode, an experimental method is shown to achieve controlled, continuous solution concentrations.