Cocrystal of Sulfamethazine and p-Aminobenzoic Acid: Structural Establishment and Enhanced Antibacterial Properties

Abstract

The engineering of pharmaceutical cocrystals has been effectively utilized to improve the physicochemical properties such as stability and solubility, and thus it could optimize the solid formations of active pharmaceutical ingredients. This work focuses on the sulfamethazine–p-aminobenzoic acid (STH–PABA) cocrystal regulated by molecular synthons constructed from mutual N···H···O interactions. The STH–PABA cocrystal was produced by means of the slow evaporation crystallization method, and the cocrystal structure was determined through X-ray crystallography. Meanwhile, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared spectroscopy, Raman, and NMR were applied to analyze the features of the STH–PABA cocrystal. Special attention was paid to in vitro antibacterial activity and microscopic investigations. Our findings indicated that the formation of cocrystals could enhance the solubility and slightly improve the release behavior of STH, and increase the leaking of bacterial cell inclusion that leads to enhanced antibacterial activity.

Eutectics and Salt of Dapsone With Hydroxybenzoic Acids: Binary Phase Diagrams, Characterization and Evaluation

“…Powder dissolution study was carried out by an RC-6 dissolution test analyzer, using the USP paddle method at a rotation speed of 100 rpm at 37 C. The known amount of the sample (1.5 g of raw drug or multicomponent solids) was added into the dissolution vessels containing 200 mL of physiological pH, including 0.1 mol/L HCL (pH ¼ 1.2), sodium acetate buffer (pH ¼ 4.5), potassium dihydrogen phosphate buffer (pH ¼ 6.8) after being sieved through 100-mesh sieves to minimize the size effect on dissolution results. At regular time intervals (2,5,10,15,20,30,45,60, 120, 240 min), 2 ml of the aliquots were withdrawn and filter through a 0.45 mm filter into the centrifuge tube and the certain amount of dissolution medium (continually heated at 37 C) was added to the dissolution vessels. A certain amount of the solution was withdrawn from centrifuge tube to chromatographic vial and diluted with chromatographic grade acetonitrile.…”

“…Sun et al 4 reported a remarkable improvement in taste and tabletability by forming a sweet salt form of metformin with acesulfame. Xu and Guan et al 5 produced sulfamethazine-p-aminobenzoic acid (STH-PABA) cocrystal which can greatly increase the antibacterial activity of STH. Lu et al 6 synthesized cocrystals of 5-fluorouracil with 3hydroxybenzoic acid, 4-aminobenzoic acid, and cinnamic acid to improve its permeability.…”

Combinations of Tautomeric Forms and Neutral-Cationic Forms in the Cocrystals of Sulfamethazine with Carboxylic Acids

“…There are examples in literature of SM cocrystals with aromatic carboxylic acid bearing the hydroxy 37 or the amino group 39 at the para-position of the ring. It was found that in the cocrystals, SM ·4-hydroxybenzoic acid as well as in the SM ·4-aminobenzoic acid a conventional V-shape structure of SM was not observed but a propeller shape was observed.…”

“…24−28 Stabilizations of amidine–imidine forms, a concept of enamine–imine equilibrium, is very common in drugs; either of the forms of a drug bearing such units are accomplished by varying crystallization conditions and by cocrystal formation. 29−39…”

Synthesis and Antibacterial Activity of New Azole, Diazole and Triazole Derivatives Based on p-Aminobenzoic Acid

“…Various compounds bearing a pABA nucleus exert strong antimicrobial [17,18], antimutagenic [19], antioxidant, cytoprotective [20], and immunomodulatory [21,22] properties. Moreover, various pABA derivatives have antineoplastic, anesthetic, antiarrhythmic, anticonvulsant, antiemetic, and gastrokinetic [16,23] properties.…”