Development and validation of a stability-indicating LC method for simultaneous determination of related compounds of guaifenesin,terbutaline sulfate and ambroxol HCl in cough syrup formulation

A new liquid chromatographic method has been developed and validated for the determination of terbutaline sulfate (TLS), guaifenesin (GFN) and ambroxol HCl (AML), for its potential impurities in drug substances and drug products. Efficient chromatographic separation was achieved on X-Terra RP-18 column with a simple mobile phase combination containing a gradient mixture of solvents A and B at a flow rate of 1.0 mL min⁻¹ and quantitation was carried out using ultraviolet detection at 222 nm with column temperature of 35 °C. The resolution between TLS, GFN and AML, its associated impurities was found to be greater than 1.5. Regression analysis shows an r value (correlation coefficient) greater than 0.998. This method was capable to detect all the process impurities of TLS, GFN and AML, at a level below 0.015% with respect to a test concentration of 0.125, 5.0 and 1.5 mg mL⁻¹, respectively. The % RSD for the inter-day and intra-day precisions for all the impurities of TLS, GFN and AML were found to be less than 3.0. The method has shown good, consistent recoveries. The drugs were subjected to stress conditions of acid, base, water hydrolysis, oxidation, photolysis and thermal degradation, as prescribed by international conference on harmonization (ICH).     

Investigation of the dynamics of radiolytic formation of ZnO nanostructured materials by pulse radiolysis

ZnO nanostructures have been synthesized by radiolytic methods. A Cobalt-60 γ-source and a 7 MeV linear electron accelerator (LINAC) was used for the radiolysis experiments. Reducing agent like hydrated electron (e_aq⁻), which is produced in radiolysis of water, was used to synthesize ZnO nanostructure materials from zinc salt. 1 M tert-butanol was used to quench the primary oxidizing radical like hydroxyl radical (OH) radiolytic water solution. Doses of about 80–130 kGy were used to perform radiolysis experiments in the present investigation. Time-resolved pulse radiolysis has been used to monitor the transient species involved in the formation of ZnO nanostructures by monitoring at different wavelengths. A scheme for the formation of the ZnO nanostructured materials by the radiolytic method has been described. The formation of ZnO nanostructures was confirmed by X-ray diffraction (XRD) measurements. Dynamic light scattering (DLS) measurements indicated that the size of the nanostructures is in the range of 6–8 nm, which is in agreement with that obtained from XRD. It is interesting to note that ZnO nanostructured materials, as prepared by the radiolytic method, exhibit strong room-temperature fluorescence.     

Experimental and computational thermodynamic study of ortho-, meta-, and para-methylbenzamide

The Knudsen mass-loss effusion technique was used to measure the vapour pressures of the three crystalline isomers of methylbenzamide. From the temperature dependence of the vapour pressures, the standard molar enthalpies of sublimation and the enthalpies of the intermolecular hydrogen bonds N−H⋯O were calculated. The temperature and molar enthalpy of fusion of the studied isomers were measured using differential scanning calorimetry. The values of the standard (p^° = 0.1 MPa) molar enthalpy of formation in the crystalline phase, at T = 298.15 K, of the compounds studied were derived from their standard massic energies of combustion measured by static-bomb combustion calorimetry. From the experimental values, the standard molar enthalpies of formation in the gaseous phase, at T = 298.15 K, were calculated and compared with the values estimated by employing computational calculations that were conducted using different quantum chemical methods: G3(MP2), G3, and CBS-QB3. Good agreement between experimental and theoretical results is verified. The aromaticity of the compounds has been evaluated through nucleus independent chemical shifts (NICS) calculations.     

Non-isothermal decomposition kinetics,thermal behavior and computational detonation properties on 4-amino-1,2,4-triazol-5-one (ATO)

The thermal behavior of 4-amino-1,2,4-triazol-5-one (ATO) was studied under non-isothermal condition by DSC method in a sealed cell of stainless steel. The melting enthalpy and melting entropy of ATO are 21.34 ± 0.49 kJ mol⁻¹ and 46.54 ± 0.30 J mol⁻¹ K⁻¹, respectively. The kinetic parameters were obtained from the analysis of DSC curves by Kissinger method, Ozawa method, the differential method and the integral method. The main exothermic decomposition reaction mechanism of ATO is classified as nucleation and growth, and the kinetic parameters of the reaction are E_a = 119.50 kJ mol⁻¹ and A = 10^9.03 s⁻¹. The gas products and condensed phase products of the thermal decomposition of ATO were studied on two simultaneous devices of the fast thermolysis reaction cell (gas reaction cell) in situ in conjunction with rapid scan transform infrared spectroscopy (RSFT-IR) and the solid reaction cell in situ. The heat of formation (HOF) for ATO was evaluated by G3 theory. The detonation velocity (D) and detonation pressure (P) were estimated by using the well-known Kamlet–Jacobs equation, based on the theoretical HOF and the determined crystal density.     

Phase transition and thermal decomposition of silver isocyanate (AgNCO)

The thermal behavior of AgNCO (silver isocyanate) has been studied via thermal analysis, optical spectroscopy, X-ray powder diffraction and transmission electron microscopy. Upon quenching the high temperature polymorph (HT-AgNCO) to room temperature, a new modification has been obtained (q-AgNCO). Its crystal structure was solved from X-ray powder diffraction data and refined by the Rietveld method (Pmmn (no. 59), a = 3.579(3) Å, b = 5.777(4) Å, c = 5.807(2) Å, V = 120.08(3) Å³, Z = 2, T = 295 K). The structure consists of chains of Ag⁺ ions bridged by isocyanate units. HT-AgNCO exists between T = 135 °C and the melting/decomposition point and exhibits virtually free rotation of the complex anions. According to preliminary single-crystal studies, HT-AgNCO (C2/m, a = 5.87 Å, b = 3.51 Å, c = 5.81 Å, ß = 105.953°, Z = 2, T = 373 K) is structurally related to α-NaN₃. The crystal structures of both, HT-AgNCO and q-AgNCO have been compared with that of the room temperature modification (RT-AgNCO). The thermal behavior and the ionic conductivity of AgNCO are discussed with respect to the related compounds AgN₃ and KSCN. Decomposition of AgNCO proceeds in distinct steps, as seen from TGA, and results in the formation of nanoparticles of elemental silver and an amorphous polymer consisting of C, N and O, only.     

Degradation of diazinon contaminated waters by ionizing radiation

Study of degradation of diazinon pesticide by ⁶⁰Co gamma irradiation in a single aqueous solution was conducted on a laboratory scale and the effect of ionizing radiation on the removal efficiency of diazinon residues was investigated. Distilled water solutions at three different concentrations of targeted compound (i.e. 0.329, 1.643 and 3.286 μmol dm⁻³) were irradiated over the range 0.1–6 kGy. The initial concentration of contaminant and irradiation doses play a significant role in the rate of destruction; this was evident from the calculated decay constants of diazinon residue. Gamma radiolysis showed that the absorbed doses from 1.5 to 5.6 kGy at a dose rate of 4.79 kGy h⁻¹ achieved 90% destruction for diazinon with initial concentrations over the range 0.329–3.286 μmol dm⁻³. The radiolytic degradation by-products and their mass balances were qualitative determined with good confidence by using GC/quadrupole mass spectrometry (GC/MS) with EI⁺ or CI in positive and negative ionization mode and diazinon degradation pathways were proposed. Additionally, the final products of irradiation were identified by ion chromatography (IC) to be acetic and formic acid.     

Oxidative thermal degradation of LDPE and the determination of some thermodynamic quantities

The pyrolysis of polyolefin wastes is one of the possible ways to obtain chemical feedstocks. In this work, the thermal degradation of low density polyethylene, (LDPE), which is a major product within plastics, was investigated in a semi-batch reactor system. First-order rate kinetics approach was chosen and reaction rate coefficients, k, and some thermodynamic quantities determined such as activation energy, reaction enthalpy, free activation enthalpy, and entropy of degradation of LDPE for different air flow rates. We found that the maximum value of some thermodynamic quantities, such as reaction rate coefficient is 0.0243 min⁻¹ at 600 mL min⁻¹ air flow rate and the free activation enthalpy (ΔG^≠) is 148.66 kJ mol⁻¹ at 450 mL min⁻¹ air flow rate and the reaction enthalpy (ΔH^≠) is 57.65 J mol⁻¹ at 623 K temperature conditions. Moreover, we found that the oxidative degradation of LDPE is not spontaneous and has lower energy necessary (for degradation) than non-oxidative degradation processes.     

Thermodynamic properties of 4-amino-3-furazanecarboxamidoxime

4-Amino-3-furazanecarboxamidoxime (AAOF) is an important precursor for synthesizing new furazano (furoxano) energetic compounds. Its thermal behaviour was studied under a non-isothermal condition by DSC methods. The results of this study show that there are one melting process and two exothermic decomposition processes. Its kinetic parameters of the intense exothermic decomposition process are obtained from analysis of the DSC curves. The apparent activation energy (E_a), pre-exponential factor (A) and the mechanism function (f(α)) were (146 ± 18) kJ · mol⁻¹, (10^10.9±1.8) s⁻¹ and (1 − α)², respectively. The specific molar heat capacity (C_p,m) of AAOF was determined by a continuous C_p mode of micro-calorimeter. The self-accelerating decomposition temperature (T_SADT), thermal ignition temperature (T_TIT) and critical temperatures of thermal explosion (T_b) were obtained to evaluate its thermal safety.     

On the electrodialysis of aqueous H2SO4–CuSO4 electrolytes with metallic impurities

This work aims to contribute to the characterization of the electrodialysis (ED) of aqueous sulfuric acid–copper sulfate solutions. The presence of impurities such as As and Sb, typical of copper electrorefining electrolytes, is also studied. Results from kinetic studies carried out in ED cells with and without re-circulation are presented. The concentrations were: 3–9 g l⁻¹ copper, 50 g l⁻¹ sulfuric acid, 3 g l⁻¹ arsenic and 0.025 g l⁻¹ antimony; the temperatures, 22 and 44 °C; the transport rates, depending on experimental conditions, 0.2–0.6 mol h⁻¹ m⁻²of membrane for copper, 0.65–2.8 for sulfate, and 0.016–0.03 for arsenic. A speciation model has been developed and applied in order to interpret the experimental results and the performance of the studied cells has been evaluated. The main conclusion is that ED can be applied to the separation and concentration of chemical species in these systems.     

The decontamination of industrial casein and milk powder by irradiation

The efficacy of gamma radiation decontamination of industrial casein, a milk protein utilized as a component of many food and non-food products has been studied. Low-fat milk powder was also included with a purpose to study the microflora survival in protein-rich materials. Microbial analysis of the samples prior to irradiation showed that the initial total viable count was higher than 6.0 log cfu g⁻¹ in both casein and milk powders. The contamination of casein with moulds and yeasts was found to be equal to 3.56 log cfu g⁻¹. The counts of coliforms have not exceeded the value of 2.48 log cfu g⁻¹. Radiation processing of casein and milk powder has substantially reduced the microbial population of all samples. The dose of 5 kGy was sufficient to reduce the total microflora and coliforms counts to the level permitted for food products. Survivals of microorganisms were analyzed by the generalized exponential equation, SF=exp[−D/D_o)^α]. Values of an exponent, α, standing for the dispersion parameter, were equal to 0.65 and 0.70 for microorganisms contaminating casein and milk powders, respectively. The numerical value of the dispersion parameter α<1 indicates the concave dependence of a logarithm of surviving fraction versus radiation dose. No difference in microflora survival in irradiated samples tested immediately and in samples stored for 1-month after irradiation has been noticed.     

Conductivity and fluorescence studies on the micellization properties of sodium cholate and sodium deoxycholate in aqueous medium at different temperatures: Effect of selected amino acids

In order to add to the existing knowledge of aqueous solution behavior of bile salts in presence of amino acids, the micellization properties of sodium cholate (NaC) (1 to 20) mmol · kg⁻¹, and sodium deoxycholate (NaDC) (0.5 to 10) mmol · kg⁻¹ in 0.1 mol · kg⁻¹ aqueous solution of glycine, leucine, methionine, and histidine have been investigated at different temperatures (293.15 to 318.15) K at intervals of T = 5 K by using conductivity and fluorescence probe studies. The critical micelle concentration (CMC) values have been determined and elucidated in terms of hydrophobicity as well as hydrophilicity of NaC and NaDC in aqueous solution of these additives. Thermodynamic parameters of micellization viz. standard Gibbs free energy (Δ_micG^o), standard enthalpy (Δ_micH^o), and standard entropy (Δ_micS^o) have also been calculated to extract information regarding the nature of micellization of bile salts in aqueous solutions. The (enthalpy + entropy) compensation plots have been interpreted to the contribution of chemical part towards micellization or stability of the micelle formed.     

Hollow fiber supported liquid membrane: a novel technique for separation and recovery of plutonium from aqueous acidic wastes

Low plutonium content acidic waste is generated in nuclear chemical facilities. Study was initiated to develop hollow fiber supported liquid membrane (HFSLM) technique for quantitative separation and recovery of plutonium (Pu) from such wastes using tri-n-butyle phosphate (TBP) in dodecane as carrier. Hollow fiber test module was fabricated using 20 lumens of 33.91 cm² surface area and 9 cm length. After satisfactory testing of the hydrodynamic condition of the module, it was operated at a flow rate of 3 ml min⁻¹ on recycling mode with acidic waste solution containing Pu=8 mg dm⁻³, uranium=15 dm⁻³, gross β⁻=49.33 mCi dm⁻³, gross γ=15.73 mCi dm⁻³ and acidity 3 M HNO₃. In presence of various fission products, selective permeation of Pu(IV) through the bundle of hollow fiber test module was observed to be more than 90% into a stripping phase consisting 0.1 M NH₂OH·HCl in 0.3 M HNO₃. A model is presented to describe the transport mechanism and to evaluate the mass transfer coefficient. The radiation stability was also tested by exposing the membrane upto irradiation level of 1 M rad. Potentiality of the method for the selective separation of plutonium from acidic waste is, thus, clearly seen.     

Field emission investigation of single Fe-doped SnO2 wire

Tin oxide submicronwires doped with Fe element were prepared by the thermal evaporation method. Morphological and structural characterizations revealed wires with sub micron size and crystalline in nature. The field electron emission from the single Fe:SnO₂ wire was carried out in conventional field emission microscope. The Fowler–Nordheim plot obtained from I–V characteristics of the wire showed a linear behavior typical that of metal. The field enhancement factor estimated from the slope of the F–N plot is 7455 cm^?1, indicating that the field emission is from nanometric features of the emitter. A current density of 10 A/cm² has been obtained at an applied field of 4.845 × 10³ V/μm. The field emission current–time record at a current level of 1 μA for more than 3 h duration is promising for various field emissions based applications.     

The thioantimonate anion [Sb4S8]4− acting as a tetradentate ligand: Solvothermal synthesis,crystal structure and properties of {[In(C6H14N2)2]2Sb4S8}Cl2 exhibiting unusual uniaxial negative and biaxial positive thermal expansion

The new compound {[In(C₆H₁₄N₂)₂]₂Sb₄S₈}Cl₂ was prepared under solvothermal conditions reacting InCl₃, Sb and S using 1,2-trans-diaminocyclohexane as solvent and structure directing molecule. The compound crystallizes in the monoclinic space group C2/c with a = 29.0259(12), b = 6.7896(2), c = 24.2023(12) Å, β = 99.524(4)°, V = 4703.9(3) ų. The central structural motif is the thioantimonate(III) anion [Sb₄S₈]^4? acting as a tetradentate ligand thus joining two symmetry related In³⁺ centered complexes. This binding mode was never observed before for the [Sb₄S₈]^4? anion. The optical band gap was determined as 2.03 eV in agreement with the red color of the compound. The thermal decomposition was monitored with in-situ X-ray diffraction experiments. After the emission of the amine molecules an amorphous intermediate is formed followed by the crystallization of InSbS₃ which is stable up to about 590 °C. On further heating, InSbS₃ is destroyed and reflections of γ-In₂S₃ appear being contaminated with some elemental Sb. Temperature dependent in-situ X-ray powder diffractometry performed between 30 and 220 °C reveals an unusual reversible negative and positive thermal expansion. The decrease of the a-axis in the temperature range is about 0.74 Å and the increase of the c-axis ca. 0.54 Å. Interestingly, the b-axis exhibits also a thermal expansion, i.e., a biaxial positive and an uniaxial negative thermal expansion coexist which is very unusual. The relative negative expansion coefficients for the a-axis of ?194 × 10^?6K^?1 (30–120 °C) and ?82 × 10^?6K^?1 (120–220 °C) are in the region of so-called colossal thermal expansion.     

Thermodynamic properties,detonation characterisation and free radical of N-acetyl-3,3-dinitroazetidine

N-acetyl-3,3-dinitroazetidine (ADNAZ) is an important precursor for synthesizing new multinitroazetidine energetic compounds. Its thermal behaviour was studied under a non-isothermal condition by DSC and TG/DTG methods, the results show that there are one melting process and one endothermic decomposition process. The specific molar heat capacity (C_p,m) of ADNAZ was determined by a continuous C_p mode of micro-calorimeter and theoretical calculation, and the C_p,m of ADNAZ was 240.37 J · K⁻¹ · mol⁻¹ at T = 298.15 K. The detonation velocity (D) and detonation pressure (P) of ADNAZ were estimated using the nitrogen equivalent equation according to the experimental density, the value of D and P are (6685.83 ± 3.12) m · s⁻¹ and (18.36 ± 0.02) GPa, respectively. The free radical signals of ADNAZ were detected by electron spin resonance (ESR) technique, which is used to estimate its sensitivity.     

Reactivity of chlorodeoxypseudoephedrines with oxo-, thio-, and selenocyanates

Herein, the reactivity of chlorodeoxypseudoephedrine hydrochlorides with oxo-, thio-, and selenocyanate nucleophiles is reported. 1,3-Heterazolidine-2-iminium or ammonium salts were obtained stereoselectively in most cases. The hard–soft nature of the calcogen atom determines the mechanistic pathway via an S_N2 (X = O), aziridine intermediate (X = Se), or both (X = S). A simple method to synthesize stereoselectively the trans-isomer of 3,4-dimethyl-5-phenyl-oxazolidine-2-iminium chloride and the cis-isomer of 4-methyl-5-phenyl-oxazoline-2-ammonium chloride, was also found. In addition, heterazolidine-2-imines or amines were liberated from the corresponding salts [Cl⁻ or XCN⁻ (X = O, S, Se)] with aqueous NaOH. Finally, cis-3,4-dimethyl-5-phenyl-oxazolidine-2-iminium chloride, cis-4-methyl-5-phenyl-oxazoline-2-amine, and trans-4-methyl-5-phenyl-selenazoline-2-amine compounds were studied by X-ray diffraction.     

QSAR studies of some side chain modified 7-chloro-4-aminoquinolines as antimalarial agents

The quantitative structure–activity relationship (QSAR) analyses were carried out for a series of new side chain modified 4-amino-7-chloroquinolines to find out the structural requirements of their antimalarial activities against both chloroquine sensitive (HB3) and resistant (Dd2) Plasmodium falciparum strain. The statistically significant best 2D QSAR models for Dd2, having correlation coefficient (r²) = 0.9188 and cross validated squared correlation coefficient (q²) = 0.8349 with external predictive ability (pred_r²) = 0.7258 and for HB3, having r² = 0.9024, q² = 0.8089 and pred_r² = 0.7463 were developed by multiple linear regression coupled with genetic algorithm (GA–MLR) and stepwise (SW–MLR) forward algorithm, respectively. The results of the present study may be useful on the designing of more potent analogues as antimalarial agents.     

High energy induced decoloration and mineralization of Reactive Red 120 dye in aqueous solution: A steady state and pulse radiolysis study

Gamma radiation induced decoloration and degradation of aqueous solution of Reactive Red 120 dye (RR-120) have been investigated under different experimental conditions. Rate constants for the reaction of hydrated electron and hydroxyl radical with RR-120 were determined to be 1.2×10¹⁰ and 7.9×10⁹ mol^?1 dm³ s^?1, respectively, by pulse radiolysis technique. The decoloration and degradation efficiency were measured in terms of % decoloration and % TOC, respectively. Decoloration was observed to be most efficient under reducing condition, where the radiolytic yield for the decoloration of dye was determined to be 0.14 μmol/J. The extent of decoloration for both aerated and oxygen saturated solution was almost identical, whereas it decreased in N₂O saturated solution as well as N₂ saturated solution. For a solution having 10.56 μg/ml total organic carbon (TOC) at a dose of 3 kGy, 48% mineralization takes place in oxygen saturated solution whereas under aerated condition same was observed to be lowered to 38%.     

Identification of radiolytic products from N-nitrosodimethylamine and N-nitrosopyrrolidine by gas chromatography and mass spectrometry

The radiolytic products of N-nitrosodimethylamine (NDMA) and N-nitrosopyrrolidine (NPYR) dissolved in dichloromethane (DCM) were identified after gamma irradiation. The UV spectra of NDMA and NPYR indicated that irradiation reduced the typical peak of NDMA at 258 nm and NPYR at 260 nm.The major radiolytic components identified in irradiated NDMA were ethyl acetate and 2-dimethyl propanol. The irradiated NPYR dissolved in DCM and produced 2-butanone and 2-methyl-6-propyl piperidine as the major radiolytic components. 2-Methyl-6-propyl piperidine was the component detected in the greatest concentration in irradiated NPYR.     

Mutual and self-diffusion of charged porphyrines in aqueous solutions

We have investigated the diffusion properties for an ionic porphyrin in water. Specifically, for the {tetrasodium tetraphenylporphyrintetrasulfonate (Na₄TPPS) + water} binary system, the self-diffusion coefficients of TPPS⁴⁻ and Na⁺, and the mutual diffusion coefficients were experimentally determined as a function of Na₄TPPS concentration from (0 to 4) · 10⁻³ mol · dm⁻³ at T = 298.15 K. Absorption spectra for this system were obtained over the same concentration range. Molecular mechanics were used to compute size and shape of the TPPS⁴⁻ porphyrin. We have found that, at low solute concentrations (<0.5 · 10⁻³ mol · dm⁻³), the mutual diffusion coefficient sharply decreases as the concentration increases. This can be related to both the ionic nature of the porphyrin and complex associative processes in solution. Our experimental results are discussed on the basis of the Nernst equation, Onsager–Fuoss theory and porphyrin metal ion association. In addition, self-diffusion of TPPS⁴⁻ was used, together with the Stokes–Einstein equation, to determine the equivalent hydrodynamic radius of TPPS⁴⁻. By approximating this porphyrin to a disk, we have estimated structural parameters of TPPS⁴⁻. These were found to be in good agreement with those obtained using molecular mechanics. Our work shows how the self-diffusion coefficient of an ionic porphyrin in water is substantially different from the corresponding mutual-diffusion coefficient in both magnitude and concentration dependence. This aspect should be taken into account when diffusion-based transport is modelled for in vitro and in vivo applications of pharmaceutical relevance.