Multicomponent crystals of mefenamic acid-tromethamine with improved dissolution rate

Abstract

Mefenamic acid (MA) is a popular nonsteroidal anti-inflammatory drug classified into BCS class II which has a low solubility and dissolution rate in an aqueous medium. The present study aimed to improve the dissolution rate of MA by preparing multicomponent crystals with tromethamine (TM) through the solvent evaporation technique. The resulting powder was characterized for its solid-state properties and evaluated for the dissolution rate. The results showed that the powder X-ray diffraction pattern of the MA-TM binary system was different from its starting materials, indicating the formation of a new crystalline phase. The differential scanning calorimetry analysis of the MA-TM binary system showed a single and sharp endothermic peak at 110 °C, which was attributed to the melting point of MA-TM multicomponent crystals. The Fourier transform infrared spectroscopy analysis showed the occurrence of solid-state interaction involving proton transfer between MA and TM. The dissolution efficiency of MA-TM multicomponent crystal was 2.5-fold higher than the intact MA. The study concludes that the MA-TM binary system forms a salt-type multicomponent crystal. The multicomponent crystals can significantly increase its dissolution rate and is an alternative technique for modifying the physicochemical properties of active pharmaceutical ingredients.

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

“…In addition, the formation of a salt-type multi-component crystal of TMP-MA improves solubility as a result of a higher affinity in water. Salttype multi-component crystals immediately dissociate in an aqueous medium to cations and anions (Dwichandra Putra et al, 2016;Yuliandra et al, 2019;Zaini et al, 2019).…”

“…solvents or pharmaceutical excipients), arranged stoichiometrically. 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).…”

Preparation of Curcumin and Quercetin Multicomponent Crystals Via Solvent-Drop Grinding

“…25 The eutectic melting point of the optimal BM was lower than the melting point of curcumin (176.79°C) and quercetin (342.77°C), indicating a lower lattice energy which results in faster dissolution. 26,27 Thermal analysis showed a decrease in the melting point of the curcumin MC (171.74°C) (Figure 4). The decreased melting point was likely due to physical interactions between curcumin and quercetin.…”

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

“…One of the recent strategies applied to enhance physicochemical properties of active pharmaceutical compounds is by forming a multi-component crystal phase with an inert and safe coformer. This approach has shown successful improvement in solubility, dissolution rate, physical and chemical stability, and compressibility [6], [7], [8], [9], [10]. Multicomponent crystal phase between active pharmaceutical compounds and coformers could be formed due to non-covalent intermolecular interactions such as van der Waals bonds and hydrogen bonds [11].…”

“…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.…”