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. 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.

Automated summary

The study showed that the QESD crystallization technique can significantly improve the flowability and reduce storage agglomeration of metformin hydrochloride, allowing for direct compression into tablets. However, the tabletability of the material needs to be evaluated under actual production speeds, with potential solutions including reducing punch speed or using a precompression step to avoid deaeration issues caused by the porous structure of metformin agglomerates. Additionally, the influence of surfactants used in QESD crystallization on the strength of tablets produced was also analyzed due to limited literature on this topic.