Preparation and Solid-State Characterization of Dapsone Drug–Drug Co-Crystals

Abstract

Pharmaceutical co-crystals involving two active pharmaceutical ingredients are rarely revealed in the literature. In this work, crystal engineering principles were exercised to guide the design and synthesis of the Biopharmaceutics Classification System class IV drug dapsone (DAP). We reported six drug−drug co-crystals of DAP with sulfanilamide, flavone, luteolin, caffeine in 1:1 stoichiometry, caffeine in 1:2 stoichiometry, and 2(3H)-benzothiazolone. Bioactive coformers were deliberately selected. The resulting co-crystals were fully characterized by a range of analytical technologies, including X-ray powder diffraction, Fourier transform infrared spectroscopy, polarized light microscopy, differential scanning calorimetry, and thermogravimetric analysis, etc. Single-crystal structure analysis reveals that reoccurring supramolecular synthons are observed in different DAP co-crystals. Equilibrium solubility and intrinsic dissolution rates were also compared with those of the parent drug. This work expands the pharmaceutically acceptable solid forms of DAP and supplements the successful cases of drug−drug co-crystals.

Drug–Drug Molecular Salt Hydrate of an Anticancer Drug Gefitinib and a Loop Diuretic Drug Furosemide: An Alternative for Multidrug Treatment

“…28 Earlier, we reported the novel metastable polymorph of gefitinib that is isostructural to its stable crystals form and heating the same at the transition temperature converts it to thermodynamically stable crystal form. 29 We started our research work with the aim to improve the solid properties of gefitinib and develop its multi-API cocrystal, [30][31][32][33] to treat and manage the patient suffering from cancer and other diseases. Patients undergoing targeted chemotherapy with drugs such as gefitinib could generally have kidney toxicity such as renal dysfunction and nephrotic syndrome as its side effects along with common side effects such as diarrhea, rash, acne, dry skin, nausea, vomiting, and interstitial lung disease.…”

Polymorphism observed in dapsone–flavone cocrystals that present pronounced differences in solubility and stability

“…26 We recently reported a dapsone-flavone cocrystal and several other cocrystals. 27 The chemical structures of dapsone (DAP) and flavone (FLA) are presented in Scheme 1.…”

Pharmaceutical Cocrystals: An Overview

“…Thermal stability, compatibility and purity of cocrystals can be predicted by TGA analysis. The weight loss of sample mass during the TGA analysis is the indication of loss of volatile component or decomposition of cocrystal [61,108] .…”