Improving flowability and reducing storage agglomeration of metformin hydrochloride through QESD crystallization.

Metformin hydrochloride is a drug used in the treatment of type 2 diabetes and is administered orally using high-dose tablets. Due to its poor flowability and agglomeration during storage, metformin is commonly processed using an intermediate step such as granulation before the material can be compressed into tablets. Spherical crystallization is a method, which can be used to improve the flowability and tabletability of drugs and excipients. This study set out to create a simple quasi-emulsion solvent-diffusion crystallization method for the highly water-soluble metformin hydrochloride using a single solvent and antisolvent with surfactants so that a direct compression of the material can be realized. Hollow, spherical agglomerates of metformin with good flowability and reduced storage agglomeration were successfully produced using this method. The effect of different surfactants (HPMC, polysorbate 80 and sorbitane monooleate) used to stabilize the transient emulsion during crystallization as well as different system parameters on the morphology, flowability of the particles and storage agglomeration was analyzed.