Formation and Characterization of Sulfamethoxazole-Trimethoprim Cocrystal by Milling Process

Abstract

The purpose of this study was to describe and characterize co-crystal formation of sulfamethoxazole and trimethoprim. The co-crystal formation was carried out by solid state milling process. Co-crystal by solution cocrystallization and physical mixture were also prepared as a comparison. The potential co-crystalline phase was characterized by powder X-ray Diffraction (PXRD), thermal analysis differential scanning calorimetry (DSC), scanning electron microscope (SEM), and Fourier transform Infrared (FT-IR) spectroscopy. Effect of milling time on formation of co-crystal sulfamethoxazole and trimethoprim was investigated by DSC and PXRD analysis. The study showed that the milling process of sulfamethoxazole and trimethoprim in equimolar yielded the co-crystal. Intact co-crystal was obtained by solution co-crystallization with methanol. Prolongation of milling time accelerated the formation of co-crystal. Physical characterization showed that sulfamethoxazole and trimethoprim co-crystal demonstrated a unique powder X-ray diffraction, thermal and spectroscopic properties. The study concludes that the milling process induces equimolar co-crystal formation between sulfamethoxazole and trimethoprim. The transformation to co-crystalline phase is affected by milling time.

Enhancing solubility and antibacterial activity using multi-component crystals of trimethoprim and malic acid

“…A multi-component crystal phase is formed if the PXRD pattern of the binary mixture is distinct from its starting components (Karagianni et al, 2018;Thakral et al, 2018). The PXRD pattern of the present study (Figure 2) showed specific diffraction peaks of TMP, which are similar to a previous report (Zaini et al, 2017). The unique pattern of TMP-MA, which established new peaks, supports the formation of a distinct crystalline phase composed of both TMP and MA.…”

“…The molecules in the crystal lattice are bonded by non-covalent intermolecular interactions, such as hydrogen bonding Incorporating active pharmaceutical ingredients into multi-component crystals has been shown to enhance their physicochemical properties, including solubility and dissolution rate (Dwichandra Putra et al, 2018;Yuliandra et al, 2019), compressibility (Rahman et al, 2012;Paramanandana et al, 2020), physical and chemical stability (Vangala et al, 2011;Sopyan et al, 2017), bioavailability, and pharmacological effectiveness (Shete et al, 2015;Yuliandra et al, 2018). Multi-component crystals of TMP have been extensively investigated, including a cocrystal with sulfamethoxazole and salts of trimethoprim with cinnamic acid, acetic acid, formic acid, maleic acid, and mefenamic acid (Bryan et al, 1987;Prabakaran et al, 2001;Umadevi et al, 2002;Muthiah et al, 2006;Zaini et al, 2017;Bhattacharya et al, 2020). However, to the best of our knowledge, there are no reports on the formation of multi-component crystals of TMP with malic acid (MA) nor an investigation into its physicochemical properties.…”

Optimized Green Nanoemulsions to Remove Pharmaceutical Enoxacin from Contaminated Bulk Aqueous Solution

“…The technique was used to assess fusion temperature and enthalpy values. The crimped drug was heated to 400 °C at the heating rate of 10 °C/min as per the method adopted before . After completion of the maximum temperature, the system was cooled by purging with nitrogen gas (60 mL/min). , …”

Multicomponent Crystal of Trimethoprim and Citric Acid: Solid State Characterization and Dissolution Rate Studies

“…, the C=N group from 1636.70 cm −1 to 1589.37 cm −1 and the C=H group from 1464.00 to 1452.42 cm −1 . dissolution rate and solubility of trimethoprim through multicomponent crystalline phase with several excipients [12], [13], [14], [15], [16], [17], [24]. S ome factors may contribute to the increment of solubility and dissolution rate of multicomponent crystals of trimethoprim and citric acid.…”

“…Several multi-component crystal phases of trimethoprim include cocrystals, some of which have been reported including salts with sulfamethoxazole, mefenamic acid, cinnamic acid, formic acid, acetic acid, malic acid, and maleic acid [8], [12], [13], [14], [15], [16], [17]. However, so far there has been no report of multicomponent crystal phases of trimethoprim with citric acid.…”