Formation and Characterization of Multicomponent Crystal of Trimethoprim and Mandelic Acid by Solvent Drop Grinding Method

Abstract

Objective: To increase the solubility of trimethoprim by forming multicomponent crystals using mandelic acid as a coformer.
 Methods: Multicomponent crystals of trimethoprim and mandelic acid were prepared at a ratio of 1:1 mol by the Solvent Drop Grinding (SDG) method. Solid state characterization was carried out using Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), Fourier Transform Infrared (FTIR) spectroscopy, Scanning Electron Microscope (SEM), and polarized microscope. The solubility test of trimethoprim was carried out in CO2-free distilled water using a sonicator for 5 min and then determined by High-Performance Liquid Chromatography (HPLC) using acetonitrile and phosphoric acid in a 10:90 ratio as the mobile phase and octadecylsilane (C18) as the stationary phase.
 Results: The results showed a decrease in the melting point and enthalpy of fusion on the DSC thermogram, a new peak in the X-ray diffraction pattern, and a slight shift of wave number in the FTIR spectroscopy. Those characterizations indicated that the multicomponent crystal formed a salt type. SEM analysis showed morphological changes and formation of new crystal habits. The polarization microscopy analysis showed birefringent with various colors in all samples. The solubility of multicomponent crystal is 2.73-times higher compared to intact trimethoprim.
 Conclusion: The formation of cocrystals of trimethoprim and mandelic acid by SDG method increased the solubility of trimethoprim.

Preparation of Spray-Dried Multicomponent Crystals of Trimethoprim-Mandelic Acid and Its Physicochemical Characterization

“…1. the changes in the crystal lattice that occur due to the solid-state interaction between trimethoprim and mandelic acid molecules [13]. The type of multicomponent crystal formed in this research was likely the salt-type crystal according to the pKa rules [13,23].…”

“…Previous studies related to the formation of multicomponent crystals of trimethoprim have been investigated, including the formation of trimethoprim-sulfamethoxazole [10], trimethoprim-citric acid [11], and trimethoprim-maleic acid [12]. Our previous study also showed an improvement in trimethoprim solubility using mandelic acid as the co-former by solvent drop grinding method, which increased about 2.73 times [13].…”

“…A pharmaceutical active ingredient's melting point is related to the crystalline phase's lattice energy [25]. The decrease in the melting point resulting from intramolecular interactions between trimethoprim and mandelic acid, which leads to changes in the structure and crystallinity of the multicomponent crystals compared to intact trimethoprim [11,13].…”

Natural wound dressing films prepared from acetylated starch/κ-carrageenan blend incorporated with mandelic acid

“…When MA was incorporated into (AS-30CAR-MA) films, the new diffracted peaks were observed at 2θ values of 9.5° and 28.6° and these diffracted peaks confirmed the presence of MA in the film [34]. With the increasing amount of MA, it was observed that the peak intensity at 2θ of 9.5° and 28.6° was slightly increased while the intensity of the peak at 2θ of 20.2° was decreased.…”