Thermodynamic approaches for the prediction of oral drug absorption

The present study is a comparative study of three equations, namely the Clausius–Clapeyron, Van’t Hoff and Hildebrand (to calculate crystal–liquid fugacity ratio (CLFR) of drug compounds), to select the best model in predicting the intestinal absorption and develop a new classification system based on dose number (D _o) and CLFR. The required thermodynamic parameters [melting point, enthalpy of fusion (ΔH _m) and the differential molar heat capacity (?C _pm)] were experimentally obtained by differential scanning calorimetry. Pharmacokinetic data [the human intestinal absorption (F _a) and apparent permeability of Caco-2 (P _app _Caco-2)] and D _o were obtained from the literature. The highest value of CLFR was found for diclofenac with the value of 88.78, 87.29, and 87.84 mol% from Clausius–Clapeyron, Van’t Hoff, and Hildebrand approaches, respectively. The lowest CLFR value was seen for memantine with the value of 14.3 × 10^?17 and 26 × 10^?12 mol% from Van’t Hoff and Hildebrand equations, respectively. Statistical comparison with the Wilcoxon signed rank test showed that the CLFR values calculated by three equations are different. CLFR values of more than 1 mol% correspond to the complete intestinal absorption (F _a). There was a sigmoidal dependency between CLFR and F _a, similar to the dependency between P _app _Caco-2 and F _a. In these modeling, the excellent correlations were obtained in all three models as evidenced by a good coefficient of determination (r ² ) without a significant difference in the average absolute error. A new classification system from Hildebrand model based on D _o and CLFR was developed and was in agreement with the biopharmaceutics classification system (70.5%) and the biopharmaceutical drug disposition system (65.6%). This modeling approach can be a valuable tool for scientists as an alternative for intestinal permeability in the biopharmaceutical classification system to develop new oral drugs. The CLFR obtained from Hildebrand model is also more convenient than the Clausius Clapeyron model, because the former does not need to calculate ?C _pm (difficult step in calculating CLFR) for drug compounds. This new classification can help to develop the new drug product in industrial and academic research, without necessary in vivo experiments.     

Encapsulation of Vitamin B12 by Complex Coacervation of Whey Protein Concentrate–Pectin; Optimization and Characterization

Vitamin B₁₂ (VB₁₂) is one of the essential vitamins for the body, which is sensitive to light, heat, oxidizing agents, and acidic and alkaline substances. Therefore, the encapsulation of VB₁₂ can be one of the ways to protect it against processing and environmental conditions in food. In this work, the influence of pectin concentration (0.5–1% w/v), whey protein concentrate (WPC) level (4–8% w/v) and pH (3–9) on some properties of VB₁₂-loaded pectin–WPC complex carriers was investigated by response surface methodology (RSM). The findings showed that under optimum conditions (1:6.47, pectin:WPC and pH = 6.6), the encapsulation efficiency (EE), stability, viscosity, particle size and solubility of complex carriers were 80.71%, 85.38%, 39.58 mPa·s, 7.07 µm and 65.86%, respectively. Additionally, the formation of complex coacervate was confirmed by Fourier-transform infrared (FTIR) spectroscopy and atomic force microscopy (AFM). In addition, it was revealed that the most important factor in VB₁₂ encapsulation was pH; at a pH < isoelectric point of WPC (pH = 3), in comparison with higher pH values (6 and 9), a stronger complex was formed between pectin and WPC, which led to an increase in EE, lightness parameter, particle size and water activity, as well as a decrease in the zeta-potential and porosity of complex carriers.     

Nanomolar determination of hydrazine by TiO2 nanoparticles modified carbon paste electrode

In the present paper, the use of a novel carbon paste electrode modified by N,N′(2,3-dihydroxybenzylidene)-1,4-phenylene diamine (DHBPD) and TiO₂ nanoparticles prepared by a simple and rapid method for the determination of hydrazine (HZ) was described. In the first part of the work, cyclic voltammetry was used to investigate the redox properties of this modified electrode at various solution pH values and at various scan rates. A linear segment was found with a slope value of about 48 mV/pH in the pH range 2.0–12.0. The apparent charge transfer rate constant (k _s) and transfer coefficient (α) for electron transfer between DHBPD and TiO₂ nanoparticles-modified carbon paste electrode were calculated. In the second part of the work, the mediated oxidation of HZ at the modified electrode was described. It has been found that under optimum condition (pH 8.0) in cyclic voltammetry, a high decrease in overpotential occurs for oxidation of HZ at the modified electrode. The values of electron transfer coefficients (α) and diffusion coefficient (D) were calculated for HZ, using electrochemical approaches. Differential pulse voltammetry exhibited a linear dynamic range from 1.0 × 10⁻⁸ to 4.0 × 10⁻⁶ M and a detection limit (3σ) of 9.15 nM for HZ. Finally, this method was used for the determination of HZ in water samples, using standard addition method.     

Poly(N‐bromobenzene‐1,3‐disulfonamide) and N,N,N′,N′‐tetrabromobenzene‐1,3‐disulfonamide as a mild and efficient catalyst for chemoselective thioacetalization of carbonyl functions and transthioacetalization reactions

Poly(N‐bromobenzene‐1,3‐disulfonamide) and N,N,N′,N′‐tetrabromobenzene‐1,3‐disulfonamide are effective catalysts for chemoselective dithioacetalization of aldehydes in the presence of ketones under neutral conditions. J. Heterocyclic Chem., (2011).     

PEG‐DIL‐based MnCl42−: A novel phase transfer catalyst for nucleophilic substitution reactions of benzyl halides

Poly(ethylene glycol) dicationic ionic liquid‐based MnCl₄^2? was prepared by nucleophilic substitution of poly(ethylene glycol) dichloride with methylimidazole followed by reaction with MnCl₂. The structural properties of the catalyst were systematically investigated using Fourier transform infrared, UV–visible and Raman spectra and thermogravimetric analysis. The application of this catalyst allows the synthesis of a variety of benzyl thiocyanates and azides in high yield under reflux conditions in water. The main advantages of this method are its easy nature, rapidity, environmental benignity and high yields.     

Thermo-physical and stability properties of raw and functionalization of graphene nanoplatelets-based aqueous nanofluids

This research aimed to evaluate the thermal viscosity, stability, conductivity and density of coolants including PEG-functionalized graphene nanoplatelets (GNPs) and gum Arabic (GA)-treated GNPs as a base fluid at various temperatures and concentrations. The present study explores the impacts of GNPs functionalized with poly ethylene glycol (PEG) on the colloidal stability and thermophysical properties of water-based PEG-functionalized GNPs suspensions as a new generation of heat transfer fluids. To this end, PEG-functionalized GNPs as a covalent sample and GA-treated GNPs were synthesized and their colloidal stabilities were traced via UV–vis spectrometry. After functionalized, colloidal stability results indicate less sedimentation for covalent samples (less than 10%) that that of noncovalent one (almost 20%) after a 15-day period. In addition, all the thermophysical properties e.g. thermal conductivity, density and viscosity were measured experimentally. Further, it has shown that by loading PEG-functionalized GNPs in the water, the increasing rate of the density and viscosity is not significant, while water-based GA-treated GNPs nanofluids showed higher rates of increase. Interestingly, the water-based PEG-functionalized GNP nanofluids at very low concentration significantly increase the thermal conductivity in comparison with that of non-covalent nanofluid at the same concentration and temperature and defiantly water.     

A spectrophotometric and thermodynamic study of the charge-transfer complexes of iodine with 2-aminomethyl-15-crown-5 in chloroform and 1,2-dichloroethane solutions

Interaction of 2-aminomethyl-15-crown-5 (AM15C5) with iodine has been investigated spectrophotometrically in chloroform and 1,2-dichloroethane (1,2-DCE) solutions. The observed time dependence of the charge-transfer band and subsequent formation of I(3)(-) in solution were related to the slow transformation of the initially formed 1:1 AM15C5.I(2) outer complex to an inner electron donor-acceptor (EDA) complex, followed by fast reaction of the inner complex with iodine to form a triiodide ion. The pseudo-first-order rate constants were evaluated from the absorbance- and conductivity-time data. The stoichiometry and formation constants of the resulting EDA complexes have also been determined. Thermodynamic parameters, Delta H degrees and Delta S degrees , of the complexes have been determined from the temperature dependence of stability constants by Van't Hoff equation. The results indicate that iodine complexes of AM15C5 in both solvents are enthalpy stabilized but entropy destabilized. The influence of solvent properties on the kinetics and stability of the resulting charge-transfer complexes are discussed.     

Determination of Aluminium by Potentiometry Using Carbon Paste Ion Selective Electrode Based on N,N'-bis(salicylidene)-1,3-Propanediamine Ligand

Journal of Analytical Chemistry - A new Al3+ carbon paste ion selective electrode based on N,N'-bis(salicylidene)-1,3-propanediamine (SB-Salpr) was prepared for the quantification of trace...