Control of Crystal Aspect Ratio and Size by Changing Solvent Composition in Oiling Out Crystallization of an Active Pharmaceutical Ingredient

Abstract

Oiling out crystallization of an active pharmaceutical ingredient, API-T, was carried out under agitation using a mixed solvent (acetone/water) system, and the effects of oiling out (liquid [oily droplet phase]/liquid [continuous phase] separation) on the aspect ratio and size of crystals were investigated. Acetone composition of the oil phase and API-T distribution to the oil phase increased with a decrease in charged acetone composition, and both decreased in the continuous phase. By utilizing this relationship, API-T crystals with small aspect ratios were produced under a low charged composition of acetone, at which a high recovery of product crystals could be expected. Furthermore, large crystals were obtained in the oiling-out crystallization. Such performance was never achieved in normal single-phase crystallization, and thus an advantage of oiling out crystallization was shown.

Influence of Liquid‐Liquid Phase Separation on the Crystallization of L‐Menthol from Water

“…Additionally, recent developments demonstrated that by controlling the droplet size, as a function of the impeller's stirring speed, the crystal size could be influenced . In another case, oiling‐out has been shown to be a feasible way to attain more compact and larger crystals , providing a competitive advantage with respect to the case where oiling‐out was absent. Indeed, there is scientific evidence that oiling‐out could be a viable route for crystallization in numerous cases.…”

Investigation of the operating conditions to morphology evolution of β-l-glutamic acid during seeded cooling crystallization

“…Correspondingly, the aspect ratio used to describe the crystal shape in the references [27,28] is herein taken as a shape index, which is defined by…”

pH-dependent oiling-out during the polymorph transformation of disodium guanosine 5′-monophosphate

“…Although the oiling-out phenomenon occupied a disadvantaged position in some aspects, recent research has identified that oiling-out has its own advantages in changing the characteristics of crystals, especially in formation of new polymorphs and special structures or making amorphous substances crystalline. 18 Takasuga et al 19,20 investigated the advantages of oiling-out crystallization for obtaining large crystals. Tanaka et al 7 reported that oiling-out could be a better method for separating the mother phase and solute.…”