Mechanism of the novel antisolvent vapour precipitation (AVP) process

Ultrafine spherical maltodextrin and maltose particles were successfully produced with the Antisolvent Vapour Precipitation (AVP) technique. Comparison between lactose and maltodextrin reaffirmed that a key requirement for the process is its ability to inhibit crystallization of the material. The precipitation process consists of: (1) an initial phase separation forming an emulsion, (2) phase inversion and (3) finally a water-maltodextrin shrinkage phase which forms the spherical particles driven by interfacial surface tension. Dehydrating the droplet at different stages of the process resulted in different particle morphologies; porous, smooth, microsphere network and microspheres. Higher ethanol relative humidity, higher ethanol absolute humidity and lower initial weight concentration were found to favour the formation of amorphous microspherical particles upon drying. A unique liquid phase separation was observed which leads to the proposed particle formation mechanism for the AVP process. Further quantitative study were conducted using a newly built vapour generation system, incorporating the LabView control and monitoring system and a new humidity measurement technique based on fundamental mass and energy balance. Analysis of the mass change of the droplet throughout the AVP drying process revealed a trend which suggests that the maximum ethanol concentration within the droplet may be the prevailing factor governing microsphere formation. In addition, an interesting observation on the final solid mass recorded for the porous and microsphere network structures showed that these structures exhibit liquid retention behaviour which could be useful for encapsulation applications. In order to better understand the mechanism of the AVP process, additional research was conducted to develop an AVP drying model to describe the simultaneous absorption and evaporation of ethanol and water within the droplet. This model was developed based on fundamental heat and mass transfer analysis and the incorporation of Raoult’s Law and UNIFAC model to account for the binary interaction between water and ethanol. Comparison between the model and the experimental measurements revealed overestimation of ethanol absorption and total drying time. Further analysis suggests that this may be attributed to the counter diffusion of water and ethanol during the drying process and possibly non-Fickian diffusion behaviour of ethanol within the droplet. This work provides a fundamental basis for future work on modelling of this physical phenomenon. The mechanism and analysis provided in this work have contributed to a fundamental understanding of the AVP process in forming microspherical particles, which has potential application in drug delivery. Based on the mechanism proposed, the underlying principles of particle formation under AVP drying can be applied to other materials. The formation of porous and microsphere network, with high liquid retention behaviour suggests possible encapsulation application. In addition, the analysis and considerations employed for the AVP drying model provide a fundamental basis for further model development which would be useful in scaling up the AVP process.