Controlling the crystal structure of succinic acid via microfluidic spray-drying.

Many properties of materials, including their dissolution kinetics, hardness, and optical appearance, depend on their structure. Unfortunately, it is often difficult to control the structure of low molecular weight organic compounds that have a high propensity to crystallize if they are formulated from solutions wherein they have a high mobility. This limitation can be overcome by formulating these compounds within small airborne drops that rapidly dry, thereby limiting the time molecules have to arrange into the thermodynamically most stable phase. Such drops can be formed with a surface acoustic wave (SAW)-based spray-drier. In this paper, we demonstrate that the structure of a model low molecular weight compound relevant to applications in pharmacology and food, succinic acid, can be readily controlled with the supersaturation rate. Succinic acid particles preserve the metastable structure over at least 3 months if the initial succinic acid concentration is below 2% of its saturation concentration such that the supersaturation rate is high. We demonstrate that also the stability of the metastable phases against their transformation into the most stable phase increases with decreasing initial solute concentration and hence with increasing supersaturation rate of the spray-dried solution. These insights open up new opportunities to control the crystal structure and therefore properties of low molecular weight compounds that have a high propensity to crystallize.