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10.1021/acs.molpharmaceut.0c01096

http://scihub22266oqcxt.onion/10.1021/acs.molpharmaceut.0c01096
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33792313!8029446!33792313
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suck abstract from ncbi


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pmid33792313      Mol+Pharm 2021 ; 18 (5): 1970-1984
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  • Role of Hydrogen Bonds in Formation of Co-amorphous Valsartan/Nicotinamide Compositions of High Solubility and Durability with Anti-hypertension and Anti-COVID-19 Potential #MMPMID33792313
  • Turek M; Rozycka-Sokolowska E; Koprowski M; Marciniak B; Balczewski P
  • Mol Pharm 2021[May]; 18 (5): 1970-1984 PMID33792313show ga
  • Physicochemical properties, in particular solubility and the associated bioavailability, are key factors in determining efficacy of poorly water-soluble drugs, which constitute 40% of new drugs in the market, and improving them is an important challenge for modern pharmacy. A recent strategy to achieve this goal is formation of stable co-amorphous solid dispersions with co-formers of low molecular weight. Here, the amorphization strategy was applied for low-soluble anti-hypertensive valsartan (VAL), an angiotensin II receptor blocker, and nicotinamide, which exhibits lung- and cardio-protective effects. Through interactions with the renin-angiotensin-aldosteron system, VAL may be used to treat both hypertension and the current pandemic coronavirus SARS-CoV-2 infection. Using mechanochemical and liquid- and solid-state approaches, solvated co-amorphous solid dispersions of VAL with nicotinamide were obtained. They were characterized by spectroscopic, thermal, and X-ray analyses. The density functional theory, quantum theory of atoms in molecules, and non-covalent interaction index calculations revealed the presence of two types of hydrogen bonds between VAL and NIC (i.e., N-H...O and O-H...O). One of them had a partially covalent character, which caused conformational changes in the flexible VAL molecule, restricting contribution of the tetrazolyl N-H donor and thus limiting the possibility of co-crystal formation. The recognized VAL/NIC1- and VAL/NIC2-type heterodimeric interactions were responsible for the excellent durability of the solid compositions and up to 24-fold better solubility than VAL alone. The synthesized dispersions constitute a new class of dually acting drugs, containing an active pharmaceutical ingredient (VAL) and supporting nutraceutical (nicotinamide).
  • |*COVID-19 Drug Treatment[MESH]
  • |Angiotensin II Type 1 Receptor Blockers/*chemistry[MESH]
  • |Antihypertensive Agents/chemical synthesis/*chemistry[MESH]
  • |Biological Availability[MESH]
  • |Calorimetry, Differential Scanning[MESH]
  • |Chemistry, Pharmaceutical/*methods[MESH]
  • |Drug Carriers/*chemistry[MESH]
  • |Drug Compounding[MESH]
  • |Humans[MESH]
  • |Hydrogen Bonding[MESH]
  • |Magnetic Resonance Spectroscopy[MESH]
  • |Microscopy, Electron, Scanning[MESH]
  • |Niacinamide/*chemistry[MESH]
  • |Quantum Theory[MESH]
  • |Solubility[MESH]
  • |Spectroscopy, Fourier Transform Infrared[MESH]
  • |Valsartan/*chemistry[MESH]


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