The Experts below are selected from a list of 189 Experts worldwide ranked by ideXlab platform

Irina V Terekhova - One of the best experts on this subject based on the ideXlab platform.

  • the effect of different polymers on the solubility permeability and distribution of poor soluble 1 2 4 Thiadiazole Derivative
    Journal of Molecular Liquids, 2018
    Co-Authors: Tatyana V Volkova, A N Proshin, R S Kumeev, Ekaterina N Domanina, Irina V Terekhova
    Abstract:

    Abstract Solubility and permeability are the main parameters determining the bioavailability of drugs. In this study the increased solubility of novel 1,2,4-Thiadiazole Derivative (TDZ) proposed for the prevention and treatment of Alzheimer's disease was achieved in the solutions of polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and pluronic F127 (F127). It was found that solubilizing power of polymers follows the order F127 > PVP > PEG. The mechanism of TDZ solubilization was proposed on the basis of 1H NMR and UV-spectroscopy studies. It was suggested that PEG enhances the TDZ solubility by acting mainly as cosolvent, whereas PVP can be considered as cosolvent and complexing agent. In case of F127, the insertion of TDZ into micelles was detected. The solubilization capacity of pluronic was quantified in terms of average number of TDZ and F127 per micelle and binding constant. In order to reveal the effect of polymers on the TDZ membrane permeability, the distribution coefficients in the 1-octanol/buffer system and permeability coefficients through the novel Permeapad™ barrier were determined. The solubility-permeability and solubility-distribution relationships were discussed.

  • effects of biorelevant media components on dissolution behaviour of 1 2 4 Thiadiazole Derivative designed for alzheimerʼs disease prevention
    Chemistry & Biodiversity, 2018
    Co-Authors: Maria Promzeleva, Mikhail Chislov, Tatyana V Volkova, A N Proshin, R S Kumeev, Irina V Terekhova
    Abstract:

    : In this study, dissolution behaviour of 1,2,4-Thiadiazole Derivative (1-[5-(3-chloro-phenylamino)-1,2,4-thiadiazol-3-yl]-propan-2-ol) displaying an anti-Alzheimer activity was examined in biorelevant media such as Simulated Gastric Fluid (SGF, pH 1.2), Fasted State Simulated Gastric Fluid (FaSSGF, pH 1.6) and Fasted State Simulated Intestinal Fluid (FaSSIF, pH 6.5). It was found that solubility and dissolution rate of 1,2,4-Thiadiazole Derivative under consideration are not strongly dependent on pH, whereas these parameters are significantly affected by the buffer composition. Dissolution was found to be more effective in buffers composed of the surfactant micelles. It was demonstrated that considerable increase in solubility and dissolution rate in SGF is achieved through the interaction of 1,2,4-Thiadiazole Derivative with the micelles of sodium dodecyl sulfate. On the contrary, CMC of sodium taurochalate was shifted in the presence of 1,2,4-Thiadiazole Derivative, therefore, dissolution process is not so efficient in FaSSIF. Interactions occurring between 1,2,4-Thiadiazole Derivative and the components of biorelevant media were investigated in detail by means of UV/VIS spectroscopy, 1 H-NMR and phase solubility methods.

  • improved biopharmaceutical properties of oral formulations of 1 2 4 Thiadiazole Derivative with cyclodextrins in vitro and in vivo evaluation
    ACS Biomaterials Science & Engineering, 2018
    Co-Authors: Maria Promzeleva, Tatyana V Volkova, A N Proshin, A S Mazur, Peter M Tolstoy, Oleg Siluykov, Sergey Ivanov, Felix Kamilov, Irina V Terekhova
    Abstract:

    The synthesized 1,2,4-Thiadiazole Derivative displaying biological activity has low aqueous solubility and dissolution rate. Novel oral formulations of Thiadiazole with β- and hydroxypropyl-β-cyclodextrins were obtained by grinding and freeze-drying methods with the purpose to improve the aqueous solubility. Complex formation of 1,2,4-Thiadiazole Derivative with cyclodextrins was confirmed by means of solid-state 13C MAS CP/TOSS NMR. Solubility, dissolution rate and permeability of the solid inclusion complexes were evaluated in different biorelevant media (SGF, FaSSGF, FaSSIF) simulating the conditions in the gastrointestinal tract. It was demonstrated that the content of biorelevant media affects the properties of the inclusion complexes. In particular, solubilizing effect of cyclodextrins became less pronounced when the micelles of taurocholic acid and lecithin are formed in the dissolution media. The inclusion of Thiadiazole into cyclodextrin cavity is in competition with its partitioning into the mic...

  • Cocrystal formation, crystal structure, solubility and permeability studies for novel 1,2,4-Thiadiazole Derivative as a potent neuroprotector
    European Journal of Pharmaceutical Sciences, 2017
    Co-Authors: Artem O. Surov, Tatyana V Volkova, Irina V Terekhova, Andrei V. Churakov, Alexey N. Proshin, German L. Perlovich
    Abstract:

    Abstract The cocrystallization approach has been applied to modify the poor solubility profile of the biologically active 1,2,4-Thiadiazole Derivative (TDZ). Extensive cocrystal screening with a library of coformers resulted in formation of a new solid form of TDZ with vanillic acid in a 1:1 molar ratio. The cocrystalline phase was identified and characterized by thermal and diffraction analyses including single-crystal X-ray diffraction. The energies of intermolecular interactions in the crystal were calculated by solid-state DFT and PIXEL methods. Both calculation schemes show good consistency in terms of total energy of the intermolecular interactions and suggest that the cocrystal is mainly stabilized via hydrogen bonds, which provide ca. 44% of the lattice energy. Since the cocrystal contained the hydroxybenzoic acid Derivative as a coformer, the solubility profile of the cocrystal was investigated at different pHs using eutectic concentrations of the components. Furthermore, the influence of the cocrystallization on the permeability performance of the 1,2,4-Thiadiazole through an artificial regenerated cellulose membrane was also evaluated. In addition, the thermodynamic functions of the cocrystal formation were estimated from the solubility of the cocrystal and the corresponding solubility of the pure compounds at various temperatures. The cocrystal formation process was found to have a relatively small value of the driving force (− 5.3 kJ·mol− 1). The most significant contribution to the Gibbs energy was provided by the exothermic enthalpy of formation.

  • effect of cyclodextrin complexation on solubility of novel anti alzheimer 1 2 4 Thiadiazole Derivative
    Journal of Thermal Analysis and Calorimetry, 2017
    Co-Authors: Maria Brusnikina, Mikhail Chislov, Tatyana V Volkova, A N Proshin, Oleg Silyukov, A S Mazur, Peter M Tolstoy, Irina V Terekhova
    Abstract:

    New 1,2,4-Thiadiazole Derivative displaying neuroprotective potential and high activity in the treatment of Alzheimer’s disease has been synthesized. The objective of this study was to improve the aqueous solubility of this drug-like compound by means of complex formation with native and hydroxypropylated β-cyclodextrins. To this end, aqueous solubility of 1,2,4-Thiadiazole Derivative was investigated in the presence of β-cyclodextrins. It was shown that the phase solubility diagrams are of Bs type demonstrating the initial increase in Thiadiazole solubility in solutions of cyclodextrins (concentration up to 0.01 mol kg−1) followed by a solubility decrease due to the precipitation of the complexes formed. In comparison with β-cyclodextrin, hydroxypropyl-β-cyclodextrin displays more pronounced solubilizing action since it forms more stable complexes with Thiadiazole. Solid complexes of 1,2,4-Thiadiazole Derivative with β-cyclodextrins were prepared by grinding and freeze-drying methods. DSC, TG, hot-stage microscopy, solid-state 13C MAS CP/TOSS NMR, powder X-ray diffractometry and FTIR spectroscopy were used to prove the existence of complexes in the solid state. Solubility of the obtained formulations was also examined. It was found that complexes of Thiadiazole with hydroxypropyl-β-cyclodextrin exhibited higher solubility in phosphate buffer (pH 7.4) compared with pure Thiadiazole and its complexes with β-cyclodextrin.

Tatyana V Volkova - One of the best experts on this subject based on the ideXlab platform.

  • the effect of different polymers on the solubility permeability and distribution of poor soluble 1 2 4 Thiadiazole Derivative
    Journal of Molecular Liquids, 2018
    Co-Authors: Tatyana V Volkova, A N Proshin, R S Kumeev, Ekaterina N Domanina, Irina V Terekhova
    Abstract:

    Abstract Solubility and permeability are the main parameters determining the bioavailability of drugs. In this study the increased solubility of novel 1,2,4-Thiadiazole Derivative (TDZ) proposed for the prevention and treatment of Alzheimer's disease was achieved in the solutions of polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and pluronic F127 (F127). It was found that solubilizing power of polymers follows the order F127 > PVP > PEG. The mechanism of TDZ solubilization was proposed on the basis of 1H NMR and UV-spectroscopy studies. It was suggested that PEG enhances the TDZ solubility by acting mainly as cosolvent, whereas PVP can be considered as cosolvent and complexing agent. In case of F127, the insertion of TDZ into micelles was detected. The solubilization capacity of pluronic was quantified in terms of average number of TDZ and F127 per micelle and binding constant. In order to reveal the effect of polymers on the TDZ membrane permeability, the distribution coefficients in the 1-octanol/buffer system and permeability coefficients through the novel Permeapad™ barrier were determined. The solubility-permeability and solubility-distribution relationships were discussed.

  • effects of biorelevant media components on dissolution behaviour of 1 2 4 Thiadiazole Derivative designed for alzheimerʼs disease prevention
    Chemistry & Biodiversity, 2018
    Co-Authors: Maria Promzeleva, Mikhail Chislov, Tatyana V Volkova, A N Proshin, R S Kumeev, Irina V Terekhova
    Abstract:

    : In this study, dissolution behaviour of 1,2,4-Thiadiazole Derivative (1-[5-(3-chloro-phenylamino)-1,2,4-thiadiazol-3-yl]-propan-2-ol) displaying an anti-Alzheimer activity was examined in biorelevant media such as Simulated Gastric Fluid (SGF, pH 1.2), Fasted State Simulated Gastric Fluid (FaSSGF, pH 1.6) and Fasted State Simulated Intestinal Fluid (FaSSIF, pH 6.5). It was found that solubility and dissolution rate of 1,2,4-Thiadiazole Derivative under consideration are not strongly dependent on pH, whereas these parameters are significantly affected by the buffer composition. Dissolution was found to be more effective in buffers composed of the surfactant micelles. It was demonstrated that considerable increase in solubility and dissolution rate in SGF is achieved through the interaction of 1,2,4-Thiadiazole Derivative with the micelles of sodium dodecyl sulfate. On the contrary, CMC of sodium taurochalate was shifted in the presence of 1,2,4-Thiadiazole Derivative, therefore, dissolution process is not so efficient in FaSSIF. Interactions occurring between 1,2,4-Thiadiazole Derivative and the components of biorelevant media were investigated in detail by means of UV/VIS spectroscopy, 1 H-NMR and phase solubility methods.

  • improved biopharmaceutical properties of oral formulations of 1 2 4 Thiadiazole Derivative with cyclodextrins in vitro and in vivo evaluation
    ACS Biomaterials Science & Engineering, 2018
    Co-Authors: Maria Promzeleva, Tatyana V Volkova, A N Proshin, A S Mazur, Peter M Tolstoy, Oleg Siluykov, Sergey Ivanov, Felix Kamilov, Irina V Terekhova
    Abstract:

    The synthesized 1,2,4-Thiadiazole Derivative displaying biological activity has low aqueous solubility and dissolution rate. Novel oral formulations of Thiadiazole with β- and hydroxypropyl-β-cyclodextrins were obtained by grinding and freeze-drying methods with the purpose to improve the aqueous solubility. Complex formation of 1,2,4-Thiadiazole Derivative with cyclodextrins was confirmed by means of solid-state 13C MAS CP/TOSS NMR. Solubility, dissolution rate and permeability of the solid inclusion complexes were evaluated in different biorelevant media (SGF, FaSSGF, FaSSIF) simulating the conditions in the gastrointestinal tract. It was demonstrated that the content of biorelevant media affects the properties of the inclusion complexes. In particular, solubilizing effect of cyclodextrins became less pronounced when the micelles of taurocholic acid and lecithin are formed in the dissolution media. The inclusion of Thiadiazole into cyclodextrin cavity is in competition with its partitioning into the mic...

  • Cocrystal formation, crystal structure, solubility and permeability studies for novel 1,2,4-Thiadiazole Derivative as a potent neuroprotector
    European Journal of Pharmaceutical Sciences, 2017
    Co-Authors: Artem O. Surov, Tatyana V Volkova, Irina V Terekhova, Andrei V. Churakov, Alexey N. Proshin, German L. Perlovich
    Abstract:

    Abstract The cocrystallization approach has been applied to modify the poor solubility profile of the biologically active 1,2,4-Thiadiazole Derivative (TDZ). Extensive cocrystal screening with a library of coformers resulted in formation of a new solid form of TDZ with vanillic acid in a 1:1 molar ratio. The cocrystalline phase was identified and characterized by thermal and diffraction analyses including single-crystal X-ray diffraction. The energies of intermolecular interactions in the crystal were calculated by solid-state DFT and PIXEL methods. Both calculation schemes show good consistency in terms of total energy of the intermolecular interactions and suggest that the cocrystal is mainly stabilized via hydrogen bonds, which provide ca. 44% of the lattice energy. Since the cocrystal contained the hydroxybenzoic acid Derivative as a coformer, the solubility profile of the cocrystal was investigated at different pHs using eutectic concentrations of the components. Furthermore, the influence of the cocrystallization on the permeability performance of the 1,2,4-Thiadiazole through an artificial regenerated cellulose membrane was also evaluated. In addition, the thermodynamic functions of the cocrystal formation were estimated from the solubility of the cocrystal and the corresponding solubility of the pure compounds at various temperatures. The cocrystal formation process was found to have a relatively small value of the driving force (− 5.3 kJ·mol− 1). The most significant contribution to the Gibbs energy was provided by the exothermic enthalpy of formation.

  • effect of cyclodextrin complexation on solubility of novel anti alzheimer 1 2 4 Thiadiazole Derivative
    Journal of Thermal Analysis and Calorimetry, 2017
    Co-Authors: Maria Brusnikina, Mikhail Chislov, Tatyana V Volkova, A N Proshin, Oleg Silyukov, A S Mazur, Peter M Tolstoy, Irina V Terekhova
    Abstract:

    New 1,2,4-Thiadiazole Derivative displaying neuroprotective potential and high activity in the treatment of Alzheimer’s disease has been synthesized. The objective of this study was to improve the aqueous solubility of this drug-like compound by means of complex formation with native and hydroxypropylated β-cyclodextrins. To this end, aqueous solubility of 1,2,4-Thiadiazole Derivative was investigated in the presence of β-cyclodextrins. It was shown that the phase solubility diagrams are of Bs type demonstrating the initial increase in Thiadiazole solubility in solutions of cyclodextrins (concentration up to 0.01 mol kg−1) followed by a solubility decrease due to the precipitation of the complexes formed. In comparison with β-cyclodextrin, hydroxypropyl-β-cyclodextrin displays more pronounced solubilizing action since it forms more stable complexes with Thiadiazole. Solid complexes of 1,2,4-Thiadiazole Derivative with β-cyclodextrins were prepared by grinding and freeze-drying methods. DSC, TG, hot-stage microscopy, solid-state 13C MAS CP/TOSS NMR, powder X-ray diffractometry and FTIR spectroscopy were used to prove the existence of complexes in the solid state. Solubility of the obtained formulations was also examined. It was found that complexes of Thiadiazole with hydroxypropyl-β-cyclodextrin exhibited higher solubility in phosphate buffer (pH 7.4) compared with pure Thiadiazole and its complexes with β-cyclodextrin.

Singaravelu Ganesan - One of the best experts on this subject based on the ideXlab platform.

  • determination on the binding of Thiadiazole Derivative to human serum albumin a spectroscopy and computational approach
    Journal of Biomolecular Structure & Dynamics, 2016
    Co-Authors: Subramani Karthikeyan, Ganesan Bharanidharan, Karthik Ananth Mani, N Srinivasan, Manish Kesherwani, D Velmurugan, Prakasarao Aruna, Singaravelu Ganesan
    Abstract:

    4-[3-acetyl-5-(acetylamino)-2,3-dihydro-1,3,4-Thiadiazole-2-yl]phenyl benzoate from the family of Thiadiazole Derivative has been newly synthesized. It has good anticancer activity as well as antibacterial and less toxic in nature, its binding characteristics are therefore of huge interest for understanding pharmacokinetic mechanism of the drug. The binding of Thiadiazole Derivative to human serum albumin (HSA) has been investigated by studying its quenching mechanism, binding kinetics and the molecular distance, r between the donor (HSA) and acceptor (Thiadiazole Derivative) was estimated according to Forster’s theory of non-radiative energy transfer. The Gibbs free energy (ΔG), enthalpy (ΔH) and entropy (ΔS) changes of temperature-dependent Kb was calculated, which explains that the reaction is spontaneous and exothermic. The microenvironment of HSA have also been studied using synchronous fluorescence spectroscopy, and the feature of Thiadiazole Derivative-induced structural changes of HSA have been ca...

  • Determination on the binding of Thiadiazole Derivative to human serum albumin: a spectroscopy and computational approach.
    Journal of Biomolecular Structure & Dynamics, 2016
    Co-Authors: Subramani Karthikeyan, Ganesan Bharanidharan, Karthik Ananth Mani, N Srinivasan, Manish Kesherwani, D Velmurugan, Prakasarao Aruna, Singaravelu Ganesan
    Abstract:

    4-[3-acetyl-5-(acetylamino)-2,3-dihydro-1,3,4-Thiadiazole-2-yl]phenyl benzoate from the family of Thiadiazole Derivative has been newly synthesized. It has good anticancer activity as well as antibacterial and less toxic in nature, its binding characteristics are therefore of huge interest for understanding pharmacokinetic mechanism of the drug. The binding of Thiadiazole Derivative to human serum albumin (HSA) has been investigated by studying its quenching mechanism, binding kinetics and the molecular distance, r between the donor (HSA) and acceptor (Thiadiazole Derivative) was estimated according to Forster's theory of non-radiative energy transfer. The Gibbs free energy (ΔG), enthalpy (ΔH) and entropy (ΔS) changes of temperature-dependent Kb was calculated, which explains that the reaction is spontaneous and exothermic. The microenvironment of HSA have also been studied using synchronous fluorescence spectroscopy, and the feature of Thiadiazole Derivative-induced structural changes of HSA have been carried using Fourier transform infrared spectroscopy and the Molecular modelling simulations explore the hydrophobic and hydrogen bonding interactions.

A N Proshin - One of the best experts on this subject based on the ideXlab platform.

  • the effect of different polymers on the solubility permeability and distribution of poor soluble 1 2 4 Thiadiazole Derivative
    Journal of Molecular Liquids, 2018
    Co-Authors: Tatyana V Volkova, A N Proshin, R S Kumeev, Ekaterina N Domanina, Irina V Terekhova
    Abstract:

    Abstract Solubility and permeability are the main parameters determining the bioavailability of drugs. In this study the increased solubility of novel 1,2,4-Thiadiazole Derivative (TDZ) proposed for the prevention and treatment of Alzheimer's disease was achieved in the solutions of polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), and pluronic F127 (F127). It was found that solubilizing power of polymers follows the order F127 > PVP > PEG. The mechanism of TDZ solubilization was proposed on the basis of 1H NMR and UV-spectroscopy studies. It was suggested that PEG enhances the TDZ solubility by acting mainly as cosolvent, whereas PVP can be considered as cosolvent and complexing agent. In case of F127, the insertion of TDZ into micelles was detected. The solubilization capacity of pluronic was quantified in terms of average number of TDZ and F127 per micelle and binding constant. In order to reveal the effect of polymers on the TDZ membrane permeability, the distribution coefficients in the 1-octanol/buffer system and permeability coefficients through the novel Permeapad™ barrier were determined. The solubility-permeability and solubility-distribution relationships were discussed.

  • effects of biorelevant media components on dissolution behaviour of 1 2 4 Thiadiazole Derivative designed for alzheimerʼs disease prevention
    Chemistry & Biodiversity, 2018
    Co-Authors: Maria Promzeleva, Mikhail Chislov, Tatyana V Volkova, A N Proshin, R S Kumeev, Irina V Terekhova
    Abstract:

    : In this study, dissolution behaviour of 1,2,4-Thiadiazole Derivative (1-[5-(3-chloro-phenylamino)-1,2,4-thiadiazol-3-yl]-propan-2-ol) displaying an anti-Alzheimer activity was examined in biorelevant media such as Simulated Gastric Fluid (SGF, pH 1.2), Fasted State Simulated Gastric Fluid (FaSSGF, pH 1.6) and Fasted State Simulated Intestinal Fluid (FaSSIF, pH 6.5). It was found that solubility and dissolution rate of 1,2,4-Thiadiazole Derivative under consideration are not strongly dependent on pH, whereas these parameters are significantly affected by the buffer composition. Dissolution was found to be more effective in buffers composed of the surfactant micelles. It was demonstrated that considerable increase in solubility and dissolution rate in SGF is achieved through the interaction of 1,2,4-Thiadiazole Derivative with the micelles of sodium dodecyl sulfate. On the contrary, CMC of sodium taurochalate was shifted in the presence of 1,2,4-Thiadiazole Derivative, therefore, dissolution process is not so efficient in FaSSIF. Interactions occurring between 1,2,4-Thiadiazole Derivative and the components of biorelevant media were investigated in detail by means of UV/VIS spectroscopy, 1 H-NMR and phase solubility methods.

  • improved biopharmaceutical properties of oral formulations of 1 2 4 Thiadiazole Derivative with cyclodextrins in vitro and in vivo evaluation
    ACS Biomaterials Science & Engineering, 2018
    Co-Authors: Maria Promzeleva, Tatyana V Volkova, A N Proshin, A S Mazur, Peter M Tolstoy, Oleg Siluykov, Sergey Ivanov, Felix Kamilov, Irina V Terekhova
    Abstract:

    The synthesized 1,2,4-Thiadiazole Derivative displaying biological activity has low aqueous solubility and dissolution rate. Novel oral formulations of Thiadiazole with β- and hydroxypropyl-β-cyclodextrins were obtained by grinding and freeze-drying methods with the purpose to improve the aqueous solubility. Complex formation of 1,2,4-Thiadiazole Derivative with cyclodextrins was confirmed by means of solid-state 13C MAS CP/TOSS NMR. Solubility, dissolution rate and permeability of the solid inclusion complexes were evaluated in different biorelevant media (SGF, FaSSGF, FaSSIF) simulating the conditions in the gastrointestinal tract. It was demonstrated that the content of biorelevant media affects the properties of the inclusion complexes. In particular, solubilizing effect of cyclodextrins became less pronounced when the micelles of taurocholic acid and lecithin are formed in the dissolution media. The inclusion of Thiadiazole into cyclodextrin cavity is in competition with its partitioning into the mic...

  • effect of cyclodextrin complexation on solubility of novel anti alzheimer 1 2 4 Thiadiazole Derivative
    Journal of Thermal Analysis and Calorimetry, 2017
    Co-Authors: Maria Brusnikina, Mikhail Chislov, Tatyana V Volkova, A N Proshin, Oleg Silyukov, A S Mazur, Peter M Tolstoy, Irina V Terekhova
    Abstract:

    New 1,2,4-Thiadiazole Derivative displaying neuroprotective potential and high activity in the treatment of Alzheimer’s disease has been synthesized. The objective of this study was to improve the aqueous solubility of this drug-like compound by means of complex formation with native and hydroxypropylated β-cyclodextrins. To this end, aqueous solubility of 1,2,4-Thiadiazole Derivative was investigated in the presence of β-cyclodextrins. It was shown that the phase solubility diagrams are of Bs type demonstrating the initial increase in Thiadiazole solubility in solutions of cyclodextrins (concentration up to 0.01 mol kg−1) followed by a solubility decrease due to the precipitation of the complexes formed. In comparison with β-cyclodextrin, hydroxypropyl-β-cyclodextrin displays more pronounced solubilizing action since it forms more stable complexes with Thiadiazole. Solid complexes of 1,2,4-Thiadiazole Derivative with β-cyclodextrins were prepared by grinding and freeze-drying methods. DSC, TG, hot-stage microscopy, solid-state 13C MAS CP/TOSS NMR, powder X-ray diffractometry and FTIR spectroscopy were used to prove the existence of complexes in the solid state. Solubility of the obtained formulations was also examined. It was found that complexes of Thiadiazole with hydroxypropyl-β-cyclodextrin exhibited higher solubility in phosphate buffer (pH 7.4) compared with pure Thiadiazole and its complexes with β-cyclodextrin.

  • new water soluble dosage forms of 1 2 4 Thiadiazole Derivative on the basis of inclusion complexes with cyclodextrins
    Journal of Thermal Analysis and Calorimetry, 2017
    Co-Authors: Maria Brusnikina, Mikhail Chislov, Tatyana V Volkova, A N Proshin, Oleg Silyukov, Irina V Terekhova
    Abstract:

    Effect of cyclodextrins on aqueous solubility of 1-[5-(3-chloro-phenylamino)-1,2,4-thiadiazol-3-yl]-propan-2-ol (I), which was synthesized and proposed for the treatment of Alzheimer’s disease, was studied. First of all, inclusion complex formation of I with different cyclodextrins was studied in aqueous solutions. Formation of more stable complexes with β- and hydroxypropyl-β-cyclodextrins was revealed. Next, solid inclusion complexes of I with β- and hydroxypropyl-β-cyclodextrins were prepared by the mechanical grinding, and their existence in the solid state was confirmed by powder X-ray diffraction, FTIR spectroscopy, microscopy, and thermochemical methods. Dissolution testing of the tablets of pure I and its complexes with β- and hydroxypropyl-β-cyclodextrins in the aqueous buffered solutions simulated the biological environment was carried out. The observed drastic enhancement of dissolution extent and dissolution rate of the complexes was attributed to the inclusion complex formation.

German L. Perlovich - One of the best experts on this subject based on the ideXlab platform.

  • a study of the inclusion complex of bioactive Thiadiazole Derivative with 2 hydroxypropyl β cyclodextrin preparation characterization and physicochemical properties
    Journal of Molecular Liquids, 2019
    Co-Authors: Marina V Olkhovich, German L. Perlovich, Angelica V Sharapova, Svetlana V Blokhina, Sofia Ya Skachilova, E V Shilova
    Abstract:

    Abstract The main aim of this work has been to improve the solubility of bioactive 6-(acetylamino)-N-(5-ethyl-1,3,4-thiadiazol-2-yl)-hexanamide by forming an inclusion complex with 2-hydroxypropyl-β-cyclodextrin. UV–vis spectroscopy was applied to studying the host-guest interaction in the buffer solution pH 7.4. Phase solubility and Job's methods were used to confirm the formation of an inclusion complex with 1:1 stoichiometry and 103 kg·mol−1 stability constant. It has been established that in the presence of 0.069 mol·kg−1 of 2HP-β-CD, the compound solubility is equal to 11.60·10−3 mol·kg−1, which corresponds to a 7-time increase in this parameter compared to the solubility in pure buffer. The thermodynamic functions of complex formation have been determined and it has been found that the inclusion process is spontaneous and thermodynamically advantageous. Data from 1H NMR experiments also provided formation evidence of the inclusion complex between study compound and 2HP-β-CD. The inclusion complex in solid state has been obtained by grinding and characterized by differential scanning calorimetry, Fourier-transform infrared spectroscopy and X-ray diffractometry. The kinetic characteristics of dissolution process for the supramolecular complex have been obtained.

  • Cocrystals of a 1,2,4-Thiadiazole-based potent neuroprotector with gallic acid: solubility, thermodynamic stability relationships and formation pathways
    Physical Chemistry Chemical Physics, 2018
    Co-Authors: Artem O. Surov, Andrei V. Churakov, Alexey N. Proshin, Tong-bu Lu, German L. Perlovich
    Abstract:

    Three distinct solid forms, namely anhydrous cocrystals with 2 : 1 and 1 : 1 drug/acid ratios ([TDZ : GA] (2 : 1), [TDZ : GA] (1 : 1)), and a hydrated one having 1 : 1 : 1 drug/acid/water stoichiometry ([TDZ : GA : H2O] (1 : 1 : 1)), have been formed by cocrystallization of the biologically active 1,2,4-Thiadiazole Derivative (TDZ) with gallic acid (GA). The thermodynamic stability relationships between the cocrystals were rationalized in terms of Gibbs energies of the formation reactions and further verified by performing a set of competitive and exchange mechanochemical reactions. Interestingly, competitive grinding in the presence of the structurally related vanillic acid led to the formation of a new polymorphic form of the [TDZ : Vanillic acid] (1 : 1) cocrystal, which was promoted by gallic acid. The mechanochemical method was also applied to elucidate the alternative pathways of the [TDZ : GA : H2O] (1 : 1 : 1) cocrystal formation. Direct cocrystallization of TDZ with GA monohydrate was found to proceed much faster than the reaction of TDZ and anhydrous GA in the presence of an acetonitrile/water mixture, which may indicate the presence of a transitional stage. According to dissolution studies, the [TDZ : GA : H2O] (1 : 1 : 1) cocrystal was ca. 6.6 times more soluble than the parent 1,2,4-Thiadiazole at pH 2.0 and 25.0 °C. The apparent two-step dehydration behavior of the [TDZ : GA : H2O] (1 : 1 : 1) cocrystal monohydrate was clarified by analyzing the intermolecular interactions of water molecules with the crystalline environment derived from solid state DFT calculations.

  • Cocrystal formation, crystal structure, solubility and permeability studies for novel 1,2,4-Thiadiazole Derivative as a potent neuroprotector
    European Journal of Pharmaceutical Sciences, 2017
    Co-Authors: Artem O. Surov, Tatyana V Volkova, Irina V Terekhova, Andrei V. Churakov, Alexey N. Proshin, German L. Perlovich
    Abstract:

    Abstract The cocrystallization approach has been applied to modify the poor solubility profile of the biologically active 1,2,4-Thiadiazole Derivative (TDZ). Extensive cocrystal screening with a library of coformers resulted in formation of a new solid form of TDZ with vanillic acid in a 1:1 molar ratio. The cocrystalline phase was identified and characterized by thermal and diffraction analyses including single-crystal X-ray diffraction. The energies of intermolecular interactions in the crystal were calculated by solid-state DFT and PIXEL methods. Both calculation schemes show good consistency in terms of total energy of the intermolecular interactions and suggest that the cocrystal is mainly stabilized via hydrogen bonds, which provide ca. 44% of the lattice energy. Since the cocrystal contained the hydroxybenzoic acid Derivative as a coformer, the solubility profile of the cocrystal was investigated at different pHs using eutectic concentrations of the components. Furthermore, the influence of the cocrystallization on the permeability performance of the 1,2,4-Thiadiazole through an artificial regenerated cellulose membrane was also evaluated. In addition, the thermodynamic functions of the cocrystal formation were estimated from the solubility of the cocrystal and the corresponding solubility of the pure compounds at various temperatures. The cocrystal formation process was found to have a relatively small value of the driving force (− 5.3 kJ·mol− 1). The most significant contribution to the Gibbs energy was provided by the exothermic enthalpy of formation.