Molecular Salts of<scp>l</scp>-Carnosine: Combining a Natural Antioxidant and Geroprotector with “Generally Regarded as Safe” (GRAS) Organic Acids

Shemchuk, Oleksii; André, Vânia; Duarte, M. Teresa; Taddei, Paola; Rubini, Katia; Braga, Dario; Grepioni, Fabrizia

doi:10.1021/acs.cgd.7b00345

Cited by 4 publications

(5 citation statements)

References 29 publications

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“…Even though mechanochemistry encountered serious limitations in the synthesis of these forms, it was shown to be appropriate, at least for the system with fumaric acid. The folate salt may be of particular interest, and therefore, its solubility was tested, showing that it has similar solubility to that of the commercial sodium folate [ 66 ].…”

Section: Developments Of Mechanochemistry In Portugalmentioning

confidence: 99%

Mechanochemistry in Portugal—A Step towards Sustainable Chemical Synthesis

et al. 2021

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In Portugal, publications with mechanochemical methods date back to 2009, with the report on mechanochemical strategies for the synthesis of metallopharmaceuticals. Since then, mechanochemical applications have grown in Portugal, spanning several fields, mainly crystal engineering and supramolecular chemistry, catalysis, and organic and inorganic chemistry. The area with the most increased development is the synthesis of multicomponent crystal forms, with several groups synthesizing solvates, salts, and cocrystals in which the main objective was to improve physical properties of the active pharmaceutical ingredients. Recently, non-crystalline materials, such as ionic liquids and amorphous solid dispersions, have also been studied using mechanochemical methods. An area that is in expansion is the use of mechanochemical synthesis of bioinspired metal-organic frameworks with an emphasis in antibiotic coordination frameworks. The use of mechanochemistry for catalysis and organic and inorganic synthesis has also grown due to the synthetic advantages, ease of synthesis, scalability, sustainability, and, in the majority of cases, the superior properties of the synthesized materials. It can be easily concluded that mechanochemistry is expanding in Portugal in diverse research areas.

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Section: Developments Of Mechanochemistry In Portugalmentioning

confidence: 99%

Mechanochemistry in Portugal—A Step towards Sustainable Chemical Synthesis

et al. 2021

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“…Acid-base interactions may lead to solubilities exceeding the pure low-solubility APIs [36]. Various studies have reported the enhancement achieved with formulations of acid-APIs combined with basic AA, such as arginine (ARG) and lysine (LYS), which have amino groups in their side chain (see Figure 2) [34].…”

Section: Introductionmentioning

confidence: 99%

“…These groups provide a basic reactivity toward the acidic functional groups of the selected API to form a salt. Regarding the formation of salts, according to Shemchuk et al [36], a difference of 2 or more between the pKb (base) and pKa (acid) values may determine salt formation in binary formulations since the probability of a proton transfer is high, and salt formation is expected [20,36]. Most commercially available tablet formulations stumble with the dissolution of FA since these exhibit different dissolution rates and low dissolution levels, failing to meet USP (US Pharmacopeia) requirements; this severely affects the therapeutic dose needed for specific supplementation required (e.g., pregnant women with NTDs history) [17,18].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Basic Amino Acids on Folic Acid Solubility

Pérez-Carreón,

Martínez,

Videa

et al. 2023

Pharmaceutics

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To prevent neural tube defects and other cardiovascular diseases in newborns, folic acid (FA) is recommended in pregnant women. A daily dose of 600 µg FA consumption is widely prescribed for women during pregnancy and 400 µg for women with childbearing potential. FA is a class IV compound according to the Biopharmaceutics Classification System (BCS) due to its low permeability (1.7 × 10−6 cm/s) and low solubility (1.6 mg/L); therefore, it must be administered via a formulation that enhances its solubility. Studies reported in the literature have proved that co-amorphization and salt formation of a poorly soluble drug with amino acids (AA) can significantly increase its solubility. Although arginine has been used with FA as a supplement, there is no information on the effect of basic AA (arginine and lysine) on the physical and chemical properties of FA-AA binary formulations. The present study implemented a conductimetric titration methodology to find the effective molar ratio to maximize FA solubility. The results showed that a 1:2.5 FA:AA molar ratio maximized solubility for arginine and lysine. Binary formulations were prepared using different methods, which led to an amorphous system confirmed by the presence of a glass transition, broad FTIR bands, and the absence of an X-ray diffraction pattern. Results of FA:AA (1:2.5) solubility increased in the range of 5500–6000 times compared with pure FA. In addition to solubility enhancement, the binary systems presented morphological properties that depend on the preparation method and whose consideration could be strategic for scaling purposes.

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“…The Class II and IV quadrants of Biopharmaceutics Classification System (BCS) representing low solubility APIs − can be improved by the design of molecular cocrystals and salts with generally recognized as safe (GRAS) coformers . The selection of GRAS coformer for a given API is guided by the Δp K a rule. − We report newly synthesized salts and salt-cocrystals of the antibiotic drug pefloxacin (PEF) with improved physicochemical properties of high solubility and good stability.…”

Section: Introductionmentioning

confidence: 99%

Salts and Salt Cocrystals of the Antibacterial Drug Pefloxacin

Gunnam

Suresh

Nangia

2018

Crystal Growth & Design

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Pefloxacin (PEF) is an amphoteric, antibacterial drug which exists as a neutral molecule in the crystal structure stabilized by C–H···O and C–H···F interactions. The design of multicomponent solids using crystal engineering was undertaken in a cocrystal/salt screen of PEF with generally recognized as safe (GRAS) dicarboxylic acids to improve the solubility and phase stability of the drug. Ten multicomponent forms, namely, five salts, two salt hydrates, and three salt cocrystals, were prepared by liquid-assisted grinding followed by crystallization. In some cases, salt and salt cocrystals were obtained concomitantly during solution evaporative crystallization. Single crystal X-ray diffraction showed that the structures are stabilized by N+–H···O–, O–H···O, C–H···O, C–H···F, and π–π stacking interactions. The bulk phase purity of multicomponent forms was characterized by powder X-ray diffraction, spectroscopy, and thermal techniques. The salt/salt cocrystal forms exhibit a faster dissolution rate and higher solubility compared to pure PEF in pH 1.2 (acidic, like gastric environment) and pH 7 phosphate buffer media (neutral, like intestinal passage). Specifically the PEF+–SA– salt (SA = succinic acid) showed remarkably high solubility, dissolution rate, and stability compared to the other multicomponent forms and PEF neutral form. The drug formulation compatible pefloxacin succinate is a promising soluble and stable PEF salt.

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Molecular Salts ofl-Carnosine: Combining a Natural Antioxidant and Geroprotector with “Generally Regarded as Safe” (GRAS) Organic Acids

Cited by 4 publications

References 29 publications

Mechanochemistry in Portugal—A Step towards Sustainable Chemical Synthesis

Mechanochemistry in Portugal—A Step towards Sustainable Chemical Synthesis

Effect of Basic Amino Acids on Folic Acid Solubility

Salts and Salt Cocrystals of the Antibacterial Drug Pefloxacin

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