Improved Solubility and Dissolution Rate of Ketoprofen by the Formation of Multicomponent Crystals with Tromethamine

Abstract

This study aims to improve the dissolution rate of ketoprofen by preparing multicomponent crystals with tromethamine. The multicomponent crystals (equimolar ratio) of ketoprofen and tromethamine were prepared by the solvent co-evaporation method. The solid-state properties of the resulting powder were characterized by powder X-ray diffraction, DSC thermal analysis, FT–IR spectroscopy, solubility, and in vitro dissolution rate. The crystal structure of the multicomponent crystal was determined by single-crystal X-ray diffraction analysis. The results showed that the powder X-ray diffraction pattern of the ketoprofen–tromethamine binary system was different from that of the starting materials. This difference indicates the formation of a new crystalline phase between ketoprofen and tromethamine (equimolar ratio). The DSC thermogram of the ketoprofen–tromethamine binary system exhibited a single and sharp endothermic peak at 128.67 °C, attributed to the melting point of a multicomponent crystal of ketoprofen–tromethamine. A single-crystal X-ray analysis revealed that ketoprofen–tromethamine formed a layered structure, salt-type multicomponent crystal. The solubility and dissolution rate of the multicomponent crystal were notably enhanced compared to the intact ketoprofen. The ketoprofen–tromethamine binary system forms salt-type multicomponent crystals, which can significantly increase the solubility and dissolution rate.

Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen

“…Figure 4 A shows the FTIR spectra of ketoprofen, the three basic excipients, and their physical and coprecipitated mixtures. Specific IR absorption bands of pure ketoprofen detected at 1610 cm −1 and 1684 cm −1 were due to stretching of the ketone group and the carboxylic carbonyl group (C=O), respectively [ 14 ]. The characteristic peaks at their assigned wavenumbers were simply additive to the FTIR spectra of the three basic excipients, indicating that no observable physicochemical interactions could be identified with the physical mixtures.…”

“…The stability of such complexes, and their observed proximity, may favor the potential proton transfer between the ketoprofen acidic group and the guanidine amino group of arginine in a salt formation process. Recently, the salt formation between ketoprofen and tromethamine was confirmed [ 14 ]. A salt formation between ketoprofen and lysine was also described, substantiating our assumptions [ 13 ].…”

“…Both forms have enhanced dissolution characteristics, but the bitterness scores for these two forms of ketoprofen-L-lysine were higher than that of the parent drug [ 13 ]. In another study, ketoprofen–tromethamine was prepared by a coprecipitation method, resulting in a new crystalline state with significantly enhanced solubility and dissolution rates [ 14 ].…”

Preparation and Characterization of a Rifampicin Coamorphous Material with Tromethamine Coformer: An Experimental–Theoretical Study

“…The dissolution rates of RIF (mRIF = 992.34 mg), the physical mixture (RIF−TRIS (2:1) PM ) (mRIF = 921.01 mg), and coamorphous (RIF−TRIS (2:1)) (mRIF = 5457.05 mg) were determined in 900.0 mL of pH 6.80 at 37.0 ± 0.5 °C (surface area = 78.54 ± 0.80 cm 2 ) with a stirrer speed of 75 rpm using a USP apparatus II (paddle type). Aliquots (5.0 mL) of the sample were withdrawn at 0, 10,15,30,45,60,90,105,120,135,150,180,195, and 210 min. 65 The samples were filtered by a 0.45 μm cellulose membrane filter, suitably diluted, and assayed spectrophotometrically at 472 nm.…”

“…It must be inert, water-soluble, ideally qualified as GRAS (generally recognized as safe), and low molecular weight as a tromethamine (TRIS). 30 The use of TRIS to improve the RIF solubility has not yet been reported. TRIS is a highly watersoluble amino sugar with a pK a of 8.0 (Class I in BCS) and is primarily utilized in biochemistry and molecular biology as a constituent in buffer solutions.…”