Automated measurement of metastable zones for pharmaceutical compounds

It is important to know under what conditions crystals will grow but not nucleate when developing crystallization processes for the manufacture of pharmaceutical compounds. Owing to lengthy, personnel-intensive techniques, this data is often not available. In order to encourage the use of such data in the development programme an automated method of metastable zone determination is proposed. This method combines the use of a turbidity meter with an automated laboratory reactor. The validity of the automated method has been shown by reproducing a solubility curve for potassium nitrate, and in addition the effect of the turbidity meter sensitivity was studied. The method was then used successfully to measure the metastable zone for a pharmaceutical intermediate, thus providing useful information to aid the development of the crystallization process for that compound.