János Madarász

Thermal, FTIR and XRD study on some 1:1 molecular compounds of theophylline

Thermal stability and structural features of three newly synthesized 1:1 lattice compounds of theophylline (th) with ethylenediamine carbamate (enCO2), 1,10-phenanthroline (phen), and 5-sulfosalicylic acid (sa-5-SO3H) have been studied in comparison with those of the theophylline compounds with ethanolamine (ea) and salicylic acid (sa). Simultaneous TG-DTA measurements, FTIR spectroscopy and X-ray diffraction have been carried out to get information on the various structural units of these solid inclusions, especially on the actual form (molecule, anion or cation) of theophylline moieties built in. Theophyllinate and theophyllinium ions have been found in the ethanolammonium-theophyllinate (1:1) (1, eaH+⋅th-) and the theophyllinium salicylic acid 5-sulfonate monohydrate (1:1:1), (5, thH+⋅saSO−3⋅H2O), respectively. Whilst the 1:1 complexes with 1,10-phenanthroline (2, th⋅phen), ethylenediamine carbamate (3, th⋅enCO2), and salicylic acid (4, th⋅sa) contain neutral theophylline moieties associated with H-bonds. In compound (3) the zwitterion of N-(2-ammonium-ethyl)carbamate (NH3+-CH2-CH2-NH-CO-2) is present.

Plasticized Drug‐Loaded Melt Electrospun Polymer Mats: Characterization, Thermal Degradation, and Release Kinetics

Melt electrospinning (MES) was used to prepare fast dissolving fibrous drug delivery systems in the presence of plasticizers. This new method was found promising in the field of pharmaceutical formulation because it combines the advantages of melt extrusion and solvent-based electrospinning. Lowering of the process temperature was performed using plasticizers in order to avoid undesired thermal degradation. Carvedilol (CAR), a poorly water-soluble and thermal-sensitive model drug, was introduced into an amorphous methacrylate terpolymer matrix, Eudragit® E, suitable for fiber formation. Three plasticizers (triacetin, Tween® 80, and polyethylene glycol 1500) were tested, all of which lowered the process temperature effectively. Scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and Raman microspectrometry investigations showed that crystalline CAR turned into an amorphous form during processing and preserved it for longer time. In vitro dissolution studies revealed ultrafast drug dissolution of the fibrous samples. According to the HPLC impurity tests, the reduced stability of CAR under conditions applied without plasticizer could be avoided using plasticizers, whereas storage tests also indicated the importance of optimizing the process parameters during MES.

Inclusion compounds containing a drug: structure and thermal stability of the first clathrates of nitrazepam and isothiocyanato ethanol complexes of Co(II) and Ni(II)

Abstract Syntheses, crystal structures and comparative analytical investigations on the first two inclusion compounds of an antiepileptic drug, nitrazepam (1,3-dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one) are reported. The biologically active molecule forms isostructural clathrates with diaquadiethanolbis(isothiocyanato) complexes of both cobalt(II) and nickel(II) in molar ratios of 1:2 [M(NCS)2(C2H5OH)2(H2O)2]·2C15H11N3O3 (M=Co2+, 1, and M=Ni2+, 2). Detailed analyses of the structures, the secondary interactions, the neutral drug conformations, the FTIR spectra and thermal stabilities of the clathrates, in comparison with those of the crystalline nitrazepam, have been carried out. In the crystal structures there are only host–guest hydrogen bonds of O⋯H, N⋯H and S⋯H type. Owing to the comparable size of the two constituents neither host–host nor guest–guest secondary interactions occur. In the first thermal decomposition step a parallel release of ethanol and water was observed by simultaneous thermogravimetric and differential thermal analysis measurements. This indicates that some bonds of the metal complex unit and the host–guest secondary interactions in 1 and 2 are weaker than interactions in the pure drug. If an easy release of ethanol and water occurs during dissolution of 1 and 2, it might result in an improved bioavailability of the drug, which is soluble only in aqueous ethanol.

Characterization of drug-cyclodextrin formulations using Raman mapping and multivariate curve resolution.

Raman chemical imaging was used in the characterization of drug-excipient interactions between a drug and different types of cyclodextrins. Detailed analysis was carried out regarding the interactions between the active ingredient (API) and the cyclodextrins and the heterogeneity of the samples was studied using multivariate curve resolution-alternating least squares algorithm. The amount of recrystallized pure API was also estimated using the same curve resolution method. The Raman mapping results were validated via scanning electron microscopy-energy dispersive X-ray spectroscopy and X-ray powder diffraction. Raman mapping was found to be suitable to detect traces of pure crystalline API below the detection limit of X-ray powder diffraction.

Study of zinc thiocarbamide chloride, a single-source precursor for zinc sulfide thin films by spray pyrolysis

Thermal decomposition of the title compound, Zn(tu)2Cl2 (tu=thiourea), was studied up to 1200°C in dynamic inert (N2) and oxidative (air) atmospheres using simultaneous TG/DTA techniques. In addition, XRD and IR were employed ex situ to resolve the reaction mechanism and products. Cubic ZnS (sphalerite) is formed below 300°C in both atmospheres and is observed until 760°C, whereafter it transforms in nitrogen to the hexagonal ZnS (wurtzite). EGA by FTIR revealed the complexity of the decomposition reactions involving also the evolution of H2NCN, which reacts to form hexagonal ZnCN2 as revealed by an XRD analysis.

Evolved gas analysis of dichlorobis(thiourea)zinc(II) by coupled TG-FTIR and TG/DTA-MS techniques

Identification and monitoring of gaseous species released during thermal decomposition of the title compound 1, Zn(tu)2Cl2, (tu=thiourea, (NH2)2C=S) have been carried out in flowing air atmosphere up to 800°C by both online coupled TG-EGA-FTIR and simultaneous TG/DTA-EGA-MS. The first gaseous products of 1, between 200 and 240°C, are carbon disulfide (CS2) and ammonia (NH3). At 240°C, an exothermic oxidation of CS2 vapors occurs resulting in a sudden release of sulphur dioxide (SO2) and carbonyl sulphide (COS). An intense evolution of hydrogen cyanide (HCN) and beginning of the evolution of cyanamide (H2NCN) and isothiocyanic acid (HNCS) are also observed just above 240°C. Probably because of condensation and/or polymerization of cyanamide vapors on the windows and mirrors of the FTIR gas cell optics, some strange baseline shape changes are also occurring above 330°C. Above 500°C the oxidation process of organic residues appears to accelerate which is indicated by the increasing concentration of CO2, while above 600°C zinc sulfide starts to oxidize resulting in the evolution of SO2. All species identified by FTIR gas cell were also confirmed by mass spectrometry, except for HNCS.

Comparison of theophyllinato Cu(II) complexes of ethanolamine and diethanolamine. Part 2. Structure and thermal study of the dimeric complex with diethanolamine

Abstract There is now much evidence that anticancer drugs exert biological action by preferred binding of a transition metal to the N7 sites of the guanine residues of DNA. In our series of theophyllinato copper(II) complexes containing amine ligands, the structural effect of changing from ethanolamine to diethanolamine is examined. A new mixed ligand copper(II) complex, bis(μ-2-(2-hydroxyethyl)aminoethanolato-O,N,O′)bis(theophyllinato-N7)dicopper(II) (C22H34N10O8Cu2) (1) has been synthesized as model compound from aqueous solutions of CuSO4, theophylline, and diethanolamine (dea). Its distinct Me2L2L′2 structure has been determined by single crystal X-ray diffraction. The centrosymmetric binuclear complex contains two strongly distorted square pyramidally (or pseudooctahedrally) coordinated copper ions bound together by two alkoxo-bridges. The bridging O is a deprotonated oxygen of the monoalcoholate formed from diethanolamine. Both of the theophyllinate anions take part in N7/O6 chelation in the complex 1, while only one of the theophyllinate anions is able to perform it in the mononuclear complex (SPY-5-12)-(2-aminoethanol-N)(2-aminoethanol-N,O)bis(theophyllinato-N7)copper(II) dihydrate (2). The two copper(II) centres in 1 are found to be antiferromagnetically coupled. The combined thermogravimetric and evolved gas detection shows that the tridentate alcoholate anions are fragmented and evolved between 125 and 275°C, whilst the degradation of theophyllinate anions begins at 350°C. Structural, spectroscopic and thermal comparison to the previously published analogous monoethanolamine Cu(II) complex (2) is presented.

Structure and thermal behaviour of (SPY-5-12)-(2-aminoethanol-N) (2-aminoethanol-N,O)-bis(theophyllinato)copper(II)dihydrate: a model for DNA-metal interactions

Abstract The title compound (1) is obtained by mixing aqueous 2-aminoethanol solutions of theophylline and copper(II) salt. According to the single crystal data the Cu2+, ion is pentacoordinated and located in a slightly distorted square pyramidal configuration. Four short CuN bonds to two N(7) of the theophyllinate anions and to two nitrogen atoms of a monodentate and a bidentate 2-aminoethanol ligands are almost in the plane, while a longer CuO bond to oxygen of the bidentate 2-aminoethanol is in the apex at distance 2.350(8) A. When heated in air or in an inert atmosphere, 1 undergoes a five-step decomposition process studied by TG, DSC and evolved gas detection (EGD). The solid intermediates of the thermal decomposition were detected by FTIR and powder X-ray diffraction. First the water molecules then the mono- and bidentate 2-aminoethanol ligands are released in the order of their binding energy, showing a strong structure-stability correlation. Afterwards chemical degradation of theophyllinato ligands occurs and is accompanied in air by an intense oxidation process resulting in CuO formation.

Combined DTA and XRD study of sintering steps towards YAl3(BO3)(4)

Sintering processes in the Y2O3–Al2O3–B2 O3 system and its subsystems (Y2O3–B2O3 and Al2 O3–B2O3) have been investigated by using combined DTA and XRD measurements to get a better understanding of solid state chemical changes resulting in the formation of yttrium aluminum borate (YAl3(BO3)4, YAB) phase and to study the possible role and contribution of various simple borates formed also in the former processes.Two new exothermic heat effects of YBO3 formation have been detected by DTA in the Y2O3–B2O3 system between 720 and 980°C. In the Al2O3–B2O3 system a new experimental XRD profile of Al4B2O9 was observed. Formation of these borates seems to promote the nucleation of double borate YAB below 1000°C. Conversion of Al4B2O9 to Al18B4 O33 was observed after a long term (10 h) sintering at 1050°C. Similarly, an increased formation of YAB has been observed as a product of the sintering reaction between YBO3 and Al18B4O33 at 1150°C. The two latter single borates are found to be identical with the high temperature decomposition products of YAB.

Composition and thermal stability of SiO2-based hybrid materials TEOS-MTEOS system

Hybrid materials with different amounts of organics permanently bound on the inorganic network obtained in the TEOS-MTEOS (tetraethoxysilan-methyltriethoxysilan) system are used for obtaining coatings with different optical and mechanical properties. To study the thermal stability of the mentioned materials, compositions with different molar ratios of the precursors were prepared. The influence of the solvent and water amounts on the gelation process was also investigated. The gels obtained were characterised by IR spectrometry and their decomposition temperatures were determined by DTA/TG. Thermal stability of the gels is rather influenced by their composition than the conditions of the gelation process.