Precipitation of griseofulvin via impinging jets in stirred-tank reactors

Griseofulvin, a commercially available active pharmaceutical ingredient (API), was precipitated here using a solvent/anti-solvent approach in an impinging jet system placed within a stirred-tank reactor. Griseofulvin was dissolved in an acetone solution, and an aqueous solution containing a polymer (HPMC) and a surfactant (SDS) was used as anti-solvent. The impinging jet mixer consisted of two jet nozzles arranged diametrically opposed to each other and facing each other. The jet nozzles were organized in a submerged arrangement within the stirred-tank reactor. Sonication was also introduced at the point of impingement by way of a sonication probe. The effect of a number of operating parameters such as sonication power and angle of impingement of the two jets on the resulting particle size distribution and crystal structure was studied. The particle size distribution was measured using a laser diffraction particle size analyzer, and the precipitated griseofulvin crystals were analyzed using Scanning Electron Microscopy (SEM) and X-ray Diffraction (XRD) to obtain an image of the crystal shape and structure. Crystals with smaller mean particle sizes were produced when the two jets were oriented 180 degrees apart and pointed directly at each other. The introduction of ultrasonic power at the impingement point resulted in markedly smaller mean particle size and a tighter particle size distribution. The results were typically highly reproducible. The crystal structure was unaffected by different operating conditions, as shown by the X-Ray diffraction results.