Sulfamethoxazole salts: crystal structures, conformations and solubility

Oliveira, Carlos Henrique de Moura; Melo, Cristiane C. de

doi:10.1039/c9nj00586b

Cited by 14 publications

(6 citation statements)

References 34 publications

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“…The main changes are observed in the region 3500–2500 cm –1 . The observed bands are assigned in accordance with data available in the literature, i.e., the experimental and calculated spectra of DDS and protonated primary amines. − The absorptions associated with the drug’s amine groups are essential to distinguish between a protonated and neutral species. The DDS spectrum is characterized by a series of bands in the region 3460–3340 cm –1 (bands at 3455, 3397, 3369, and 3341 cm –1 ) related to the antisymmetric and symmetric NH 2 stretching modes.…”

Section: Resultssupporting

confidence: 75%

Investigating the Solubilities of the Nitrate and Isomorphous Bromide and Chloride Salts of Dapsone

deMelo¹,

Bitencourt²,

Corrêa

2020

Crystal Growth & Design

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Dapsone, the major drug for leprosy, has broader application against dermatoses, malaria, and AIDS-related diseases. Besides its antimicrobial/ antiprotozoal activity, dapsone has anti-inflammatory properties. However, because of its low aqueous solubility, the high oral doses required and associated side effects limit the tolerability and efficacy of dapsone free base. As a strategy to improve the drug's solubility, new salts of dapsone were prepared. The chloride, bromide, and nitrate salts of dapsone were completely characterized by X-ray diffraction (single and powder), spectroscopic (FT-IR), and thermal (DSC and TGA) techniques. The X-ray results revealed that dapsone chloride and dapsone bromide are isomorphous compounds. Dapsone salts decompose without melting and are thermally less stable than dapsone free base. The equilibrium solubility of dapsone salts was compared to dapsone free base in three aqueous media: HCl buffer pH 1.2, acetate buffer pH 4.5, and phosphate buffer pH 6.8. The highest solubility values were obtained in acid media, and dapsone bromide was found to be slightly more soluble than dapsone free base. The solubility values obtained for the nitrate and chloride salts of dapsone at pH 1.2 cannot be considered real, since the PXRD patterns show their total/partial conversion.

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Section: Resultssupporting

confidence: 75%

Investigating the Solubilities of the Nitrate and Isomorphous Bromide and Chloride Salts of Dapsone

deMelo¹,

Bitencourt²,

Corrêa

2020

Crystal Growth & Design

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“…The asymmetric unit of the ELT α-form crystal contain three crystallographically-independent bromine ions. The bromine ion at a general position form two charge-assisted hydrogen bonds 14) with protonated amino moieties of the methyl pyrrolidine rings (Supplementary Fig. S1a).…”

Section: Resultsmentioning

confidence: 99%

Bromine K-Edge X-Ray Absorption Near-Edge Structure Analysis on Hydrobromide-Salt Crystals and the Solid Dispersion of Active Pharmaceutical Ingredients

Suzuki

Tomita

Ito

et al. 2022

CHEMICAL & PHARMACEUTICAL BULLETIN

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Bromine K-edge X-ray absorption near-edge structure (XANES) spectroscopy analyses were used to evaluate the crystals of the active pharmaceutical ingredients, eletriptan hydrobromide, dextromethorphan hydrobromide and scopolamine hydrobromide salts and the solid dispersion of eletriptan hydrobromide. The crystals and the solid dispersion of the active pharmaceutical ingredient (API) salts could be discriminated based on the shape of the XANES spectra. The differences in the shape of XANES spectra was ascribable to the differences in the interatomic interactions of the bromine ions based on the crystal structures. Ratio of the eletriptan hydrobromide α-form crystal in mixed powders of α-form and monohydrate crystals could be quantified by the linear-combination fitting using their XANES spectra. These results indicated that the XANES spectroscopy are a potent method for evaluating the APIs of pharmaceutical formulations even at the higher energy region around the bromine K-edge of 13470 eV.

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“…It belongs to class IV of the Biopharmaceutics Classification System: i.e., it has low solubility and permeability . There are several known crystal forms of SMX, including five polymorphs, − a hemihydrate, , and a series of salts − and cocrystals. ,, Crystal structures of polymorphs I and II were determined in the early 1980s, , both of the monoclinic crystal system, with C 2/ c symmetry. In 2005, two new SMX polymorphs were discovered using different polymers as nucleation centers .…”

Section: Introductionmentioning

confidence: 99%

Hydrate vs Anhydrate under a Pressure-(De)stabilizing Effect of the Presence of Water in Solid Forms of Sulfamethoxazole

Patyk‐Kaźmierczak

Kaźmierczak

2021

Crystal Growth & Design

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An understanding of the structure–properties relationship of crystals is one of the principles of crystal engineering. It is well established that the physicochemical properties of solids, such as their temperature and pressure stability, can be modified by the diversification of the chemical composition: i.e., by the synthesis of multicomponent crystals. This method is widely used in the pharmaceutical industry in the search for novel crystal forms providing higher bioavailability and better processability during the manufacturing process. It is also crucial to thoroughly study, analyze, and compare multicomponent crystals with neat crystals to assess to what extent their properties were altered. In this work we investigate the effect of the presence of water molecules on the pressure stability of crystals, on an example of an antibiotic sulfamethoxazole in its neat form (polymorph I, SMX I) and as a hemihydrate (SMX·0.5H2O). The crystals were investigated under high pressure in a series of hydrostatic media up to ca. 4 GPa. SMX I was established to be the preferred and stable solid form of sulfamethoxazole under the studied conditions, while the compression of crystals of SMX·0.5H2O above 3.7 GPa led to a reversible isostructural solid-to-solid phase transition to phase II (named SMX hemihydrate-II). The difference between SMX hemihydrates I and II and a comparison of the pressure stability of the investigated forms of SMX are discussed in terms of intermolecular interactions, Full Interaction Maps (FIMs), structural voids, and changes in crystal density. It has been shown that lower density and less ordered molecular arrangement in crystals of SMX hemihydrate, a direct effect of the presence of water molecules, contribute to its lower pressure stability in comparison to crystals of SMX I.

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Sulfamethoxazole salts: crystal structures, conformations and solubility

Abstract: Novel salts of the antibiotic sulphamethoxazole were obtained and characterized, effectively showing enhanced solubility.

Cited by 14 publications

References 34 publications

Investigating the Solubilities of the Nitrate and Isomorphous Bromide and Chloride Salts of Dapsone

Investigating the Solubilities of the Nitrate and Isomorphous Bromide and Chloride Salts of Dapsone

Bromine K-Edge X-Ray Absorption Near-Edge Structure Analysis on Hydrobromide-Salt Crystals and the Solid Dispersion of Active Pharmaceutical Ingredients

Hydrate vs Anhydrate under a Pressure-(De)stabilizing Effect of the Presence of Water in Solid Forms of Sulfamethoxazole

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