Enabling the direct compression of metformin hydrochloride through QESD crystallization

Metformin hydrochloride is a drug used in the treatment of type 2 diabetes. It shows very poor flowability and agglomeration under storage so that a direct compression of the material into tablets has not yet been successfully realized. In a previous study the authors showed that a quasi-emulsion solvent-diffusion (QESD) crystallization technique can be used to drastically improve the flowability and reduce storage agglomeration of this drug.


Direct compression of high-dose metformin hydrochloride tablets enabled.

Tablet capping due to porous particle structure avoided through precompression step.

Surfactants used for quasi-emulsion solvent-diffusion can weaken tablets.

This study set out to evaluate whether QESD metformin hydrochloride can be directly compressed into high dose (> 89.5 % drug load) tablets without the use of an intermediary step such as granulation. The direct compression into tablets was successful, however it was important to evaluate the tabletability of the material under actual production speeds of the tablet press.

The porous structure of the metformin agglomerates lead to deaeration issues, however these could be avoided by reducing the punch speed or using a precompression step. Furthermore, the influence of surfactants used to stabilize the QESD crystallization on the strength of tablets produced was analyzed because the literature is still scarce on this topic.

Read the article here

Article information: Jerome Hansen, Peter Kleinebudde. Enabling the direct compression of metformin hydrochloride through QESD crystallization,
International Journal of Pharmaceutics, 2021. https://doi.org/10.1016/j.ijpharm.2021.120796.

You might also like