Open AccessEnhancing solubility and antibacterial activity using multi-component crystals of trimethoprim and malic acid
Author(s) -
Yori Yuliandra,
Limson Jaya Hutabarat,
Resty Ardila,
Maria Dona Octavia,
Erizal Zaini
Publication year - 2021
Publication title -
pharmacy education
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.198
H-Index - 17
eISSN - 1477-2701
pISSN - 1560-2214
DOI - 10.46542/pe.2021.212.296304
Subject(s) - solubility , powder diffraction , melting point , antibacterial activity , nuclear chemistry , differential scanning calorimetry , chemistry , fourier transform infrared spectroscopy , dissolution , solvent , materials science , crystallization , crystallography , organic chemistry , chemical engineering , genetics , thermodynamics , physics , biology , bacteria , engineering
Aim: To improve the solubility and antibacterial activity of trimethoprim (TMP) by preparing its multicomponent crystals with malic acid (MA). Methods: Multicomponent crystals of TMP-MA were prepared by solvent co-evaporation. The solid-state properties were characterised by powder X-ray diffraction (PXRD), differential thermal analysis (DTA), Fourier transform infrared (FT-IR) spectroscopy, and scanning electron microscopy (SEM) analyses. The solubility was investigated in an aqueous medium, while the antibacterial activity against Escherichia coli was investigated using the agar disk diffusion method. Results: The PXRD pattern of the TMP-MA binary system differed from the starting materials, supporting the formation of a new crystalline phase (equimolar ratio). The DTA thermogram showed a single, sharp, endothermic peak at 212.5 °C attributable to the TMP-MA multicomponent crystal's melting point. FT-IR spectroscopy showed a solid-state interaction involving proton transfer between TMP and MA. The multicomponent crystal displayed a 2.5-fold higher solubility and had increased antibacterial activity compared to TMP alone. Conclusions: The TMP-MA binary system forms salt-type multicomponent crystals that significantly increase solubility and antibacterial activity. Multicomponent crystal formation is a viable technique for modifying the physicochemical properties of active pharmaceutical ingredients.