Controlling polymorphism with membrane-based crystallizers: application to form I and II of paracetamol

The commercial paracetamol, dissolved in bidistilled water, was crystallized in static membrane crystallizers. The driving force of the membrane-assisted evaporation mechanism was varied by changing the rate of solvent evaporation and hence, the rate of variation of the supersaturation. The paracetamol crystals were analyzed by ATR-FTIR and two types of vibrational spectra were obtained. The selective crystallization was achieved by control of the solvent evaporation rate through the pores of the membranes. The specific interaction between the solute molecules and the membrane surface addressed the nucleation mechanism toward the production of the high energy form. Results show that the rate for solvent extraction and hence the rate of achievement of the supersaturation can be controlled in a membrane crystallizer.