The Effect of Different Manufacturing Processes on The Physicochemical Properties of Meropenem Trihydrate

Abstract

Meropenem trihydrate is a broad-spectrum antibiotic that is only used in hospitals for antibiotic-resistant bacterial infections. It is only commercially available as a dry powder for intravenous administration as a result of rapid hydrolysis and sensitivity to light. Our work aims to focus on monitoring changes in the physicochemical properties after exposing Meropenem powder to dissolving with different solvents, grinding, recrystallization and lyophilization, which they make the major processes that can be used during new dosage forms development. This study applied many techniques to evaluate: macroscopic changes using polarized microscope, thermal properties using Differential Scanning Calorimetry (DSC), stability of chemical and physical bonds using Fourier Transformation Infra-Red spectroscopy (FTIR), crystallinity using Powder X-Ray Diffraction (PXRD), and solubility comparison in distilled water between the meropenem powder vs the grinded one by assaying the active ingredient using High Performance Liquid Chromatography (HPLC). The results showed that the dry milling process did not affect the crystal structure and it maintained the stability of the active substance compared to other methods, in addition to improving its solubility. All other methods containing water, organic solvents or heat led to crystal instability and destruction of the chemical structure. Therefore, the development of any new pharmaceutical dosage form of Meropenem trihydrate will be determined by the possibility of applying grinding within the stages of its manufacture and avoiding the use of any solvents or high temperature.