Antisolvent crystallization of telmisartan using stainless-steel micromixing membrane contactors

Controlled continuous crystallization of the active pharmaceutical ingredient (API) telmisartan (TEL) has been conducted from TEL/DMSO solutions by antisolvent crystallization in deionized water using membrane micromixing contactors. The purpose of this work was to test stainless-steel membranes with ordered 10 μm pores spaced at 200 μm in a stirred-cell (batch, LDC-1) and crossflow (continuous, AXF-1) system for TEL formation. By controlling the feed flow rate of the API and solvent, through the membrane pores as well as the antisolvent flow, it was possible to tightly control the micromixing and with that to control the crystal nucleation and growth. Batch crystallization without the membrane resulted in an inhomogeneous crystallization process, giving a mixture of crystalline and amorphous TEL materials. The rate of crystallization was controlled with a higher DMSO content (4:1 DMSO/DI water), resulting in slower crystallization of the TEL material. Both membrane setups, stirred batch and the crossflow, yielded the amorphous TEL particles when deionized water was used, while a crystalline material was produced when a mixture of DI water and DMSO was used.