Preparation of Hydrotalcite Crystals Using Impinging Jet Mixers

Abstract The active pharmaceutical ingredient hydrotalcite (aluminium magnesium carbonate hydroxide hydrate) is an antacid marketed either as suspensions or tablets. It is necessary to have stringent control on multiple crystal properties not only due to the demand on high quality of the medicine but also as a result of the need to improving the efficiency of down-stream processing e.g. of filtration of crystals. This work investigated impinging jet mixers integrated with a stirred tank for the preparation of hydrotalcite crystals, using aluminum sulfate, sodium carbonate and porous magnesium hydroxide as the raw materials. The new process design has shown superior performance to the commonly used stirred tanks. The hydrotalcite crystals were of narrow particle size distribution, large size and bulk density, high purity, and uniform morphology. An attempt was also made at trying to develop mechanistic understanding of the reactive crystallization processes taking place inside the integrated impinging jet mixers - stirred tank equipment. Firstly the impinging jet mixers enabled generation of ultrafine aluminum hydroxide particles during the reactive precipitation between sodium carbonate and aluminum sulfate aqueous solutions . Then, the ultrafine aluminum hydroxide accumulated in the shallow layer of the porous magnesium hydroxide particles and gradually filled the porous particles under the stirring effect of the tank reactor. Meanwhile, the magnesium hydroxide gradually reacted with aluminum hydroxide to generate hydrotalcite from the surface towards the inside of the particles, and finally produced the high quality hydrotalcite crystals.