Cyclodextrin Complexation of Fenofibrate by Co-Grinding Method and Monitoring the Process Using Complementary Analytical Tools.

Solvent-free preparation types for cyclodextrin complexation, such as co-grinding, are technologies desired by the industry. However, in-depth analytical evaluation of the process and detailed characterization of intermediate states of the complexes are still lacking in areas. In our work, we aimed to apply the co-grinding technology and characterize the process. Fenofibrate was used as a model drug and dimethyl-ß-cyclodextrin as a complexation excipient. The physical mixture of the two substances was ground for 60 min; meanwhile, samples were taken. A solvent product of the same composition was also prepared. The intermediate samples and the final products were characterized with instrumental analytical tools. The XRPD measurements showed a decrease in the crystallinity of the drug and the DSC results showed the appearance of a new crystal form. Correlation analysis of FTIR spectra suggests a three-step complexation process. In vitro dissolution studies were performed to compare the dissolution properties of the pure drug to the products. Using a solvent-free production method, we succeeded in producing a two-component system with superior solubility properties compared to both the active ingredient and the product prepared by the solvent method. The intermolecular description of complexation was achieved with a detailed analysis of FTIR spectra.

Development of Solvent-Free Co-Ground Method to Produce Terbinafine Hydrochloride Cyclodextrin Binary Systems; Structural and In Vitro Characterizations.

Molecular complexation with cyclodextrins (CDs) has long been a known process for modifying the physicochemical properties of problematic active pharmaceutical ingredients with poor water solubility. In current times, the focus has been on the solvent-free co-grinding process, which is an industrially feasible process qualifying as a green technology. In this study, terbinafine hydrochloride (TER), a low solubility antifungal drug was used as a model drug. This study aimed to prepare co-ground products and follow through the preparation process of the co-grinding method in the case of TER and two amorphous CD derivatives: (2-hydroxypropyl)-ß-cyclodextrin (HPBCD); heptakis-(2,6-di-O-methyl)-ß-cyclodextrin (DIMEB). For this evaluation, the following analytical tools and methods were used: phase solubility studies, differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), hot-stage X-ray powder diffractometry (HOT-XRPD), Fourier-transform infrared (FT-IR), Raman spectroscopy, and Scanning Electron Microscopy (SEM). Furthermore, in vitro characterization (dissolution and diffusion studies) was performed in two kinds of dissolution medium without enzymes. In the XRPD and SEM studies, it was found that the co-grinding of the components resulted in amorphous products. FT-IR and Raman spectroscopies confirmed the formation of an inclusion complex through the unsaturated aliphatic chain of TER and CDs. In vitro characterization suggested better dissolution properties for both CDs and decreased diffusion at higher pH levels in the case of HPBCD.

The Structure and Thermal Properties of Solid Ternary Compounds Forming with Ca2+, Al3+ and Heptagluconate Ions.

In the present work, the structure and thermal stability of Ca-Al mixed-metal compounds, relevant in the Bayer process as intermediates, have been investigated. X-ray diffraction (XRD) measurements revealed the amorphous morphology of the compounds, which was corroborated by SEM-EDX measurements. The results of ICP-OES and UV-Vis experiments suggested the formation of three possible ternary calcium aluminum heptagluconate (Ca-Al-Hpgl) compounds, with the formulae of CaAlHpgl(OH)40, Ca2AlHpgl2(OH)50 and Ca3Al2Hpgl3(OH)90. Additional IR and Raman experiments revealed the centrally symmetric arrangement of heptagluconate around the metal ion. The increased thermal stability was demonstrated by thermal analysis of the solids and confirmed our findings.

Structural characterization of allomelanin from black oat.

The brown to black coloration found in plants is due to the melanins, which have been relatively poorly investigated among the plant pigments. The aim of this work was to study the dark pigment extracted from the black oat hull with respect to composition and structure. Ultraviolet-visible (UV-Vis) spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and Fourier transform infrared (FT-IR) spectroscopy were applied for the characterization of the pigment. UV-Vis spectroscopy revealed that the extracted material displays a broadband, structureless absorption profile a common feature of melanins. MALDI-TOF MS measurements demonstrated that oat melanin is a homopolymer built up from p-coumaric acid and consists mainly of low molecular weight (527-1499 Da) oligomers of 3-9 monomer units. The tetramer oligomer proved to be dominant. The results of the FT-IR analysis indicated that oat melanin is a fully conjugated aromatic system containing tetrasubstituted aromatic rings linked by CC coupling. The in vitro preparation of melanin from p-coumaric acid by horseradish peroxidase was performed for comparison. The resulting polymer consisted of oligomers of 4-9 monomer units similarly to those in oat melanin. However, the building blocks proved to be connected to each other via COC linkages in contrast with the CC linkages in oat melanin.

Speciation and structure of tin(II) in hyper-alkaline aqueous solution.

The identity of the predominating tin(ii)-hydroxide complex formed in hyper-alkaline aqueous solutions (0.2 ≤CNaOH≤ 12 mol dm(-3)) is determined by potentiometric titrations, Raman, Mössbauer and XANES spectroscopy, supplemented by quantum chemical calculations. Thermodynamic studies using a H2/Pt electrode up to free hydroxide concentrations of 1 mol dm(-3) showed the presence of a single monomeric complex with a tin(II) : hydroxide ratio of 1 : 3. This observation together with Raman and Mössbauer spectroscopic measurements supplemented by quantum mechanical calculations proved that the predominating complex is [Sn(OH)3](-), and that the presence of the other possible complex, [SnO(OH)](-), could not be proven with either experiments or simulations. The structure of the trihydroxidostannate(II) complex, [Sn(OH)3](-), was determined by EXAFS and was found to be independent of the applied hydroxide and tin(II) concentrations. The mean Sn-O bond distance is short, 2.078 Å, and in very good agreement with the only structure reported in the solid state. It is also shown that at pH values above 13 the speciation of the predominant trihydroxidostannate(II) complex is not affected by the presence of high concentrations of chloride ions.

Self-organization of calcium oxalate by flow-driven precipitation.

We have analyzed the emerging precipitate pattern of calcium-oxalate in a flow system. The circular symmetry is broken because of the hydrodynamic instability at the tip of the underlying gravity current. The presence of a concentration gradient maintained by the flow leads to the enrichment of the thermodynamically unstable calcium oxalate dihydrate form.

Using low-frequency IR spectra for the unambiguous identification of metal ion-ligand coordination sites in purpose-built complexes.

One of the aims of our long-term research is the identification of metal ion-ligand coordination sites in bioinspired metal ion-C- or N-protected amino acid (histidine, tyrosine, cysteine or cystine) complexes immobilised on the surface of chloropropylated silica gel or Merrifield resin. In an attempt to reach this goal, structurally related, but much simpler complexes have been prepared and their metal ion-ligand vibrations were determined from their low-frequency IR spectra. The central ions were Mn(II), Co(II), Ni(II) or Cu(II) and the ligands (imidazole, isopropylamine, monosodium malonate) were chosen to possess only one-type of potential donor group. The low-frequency IR spectra were taken of the complexes for each ion-ligand combination and the typical metal ion-functional group vibration bands were selected and identified. The usefulness of the obtained assignments is demonstrated on exemplary immobilised metal ion-protected amino acid complexes.

On the unexpected cation exchange behavior, caused by covalent bond formation between PEDOT and Cl- ions: extending the conception for the polymer-dopant interactions.

The ionic motion in connection with the redox transformation of poly(3,4-ethylenedioxythiophene) (PEDOT) conjugated polymer have been studied by both experimental-electrochemical (electrochemical quartz crystal nanobalance, EQCN) and spectroscopic (infrared spectroscopy, IR-ATR)-and theoretical methods. The observations have been completed by direct, semiquantitative analytical data, provided by energy dispersive X-ray (EDX) microanalysis. The EQCN results suggested an anomalous behavior, since only cationic movements have been observed for films deposited from chloride solutions. Chloride ions were proved to be immobile also when bulky tetrabutylammonium (Bu(4)N(+)) cations were substituted with even larger (hexadecyltrimethylammonium) cations. Since PEDOT films synthesized in the presence of other spherical, not too large anions-such as perchlorate and tetrafluoroborate-endowed mixed ion exchange behavior together with the Bu(4)N(+) cation, the possibility of a special interaction between chloride and the polymeric chain has been assumed. Semiempirical and DFT calculations indicated that chloride ions interact with the α carbon atoms of the thiophene rings of the oxidized EDOT oligomers, creating sp(3) type perturbations in the polymer chain. FTIR-ATR spectra evidenced the appearance of C-Cl bonds. Elementary analysis, performed by EDX spectroscopy with eight polymer samples at different doping levels clearly showed the permanent presence of constant amount of chlorine, independently of the oxidation state of the PEDOT layer. Finally, the presented observations call attention to the fact that unique dopant-polymer interactions during the electrochemical polymerization are of prime importance, being able to rule over conventions for the charge compensation of conjugated polymers, often solely based on steric parameters.

Ibuprofen penetration enhance by sucrose ester examined by ATR-FTIR in vivo.

The aim of this work was to investigate the skin penetration enhancer effect of a sucrose ester (SE) in an Ibuprofen (IBU) containing hydrogel and to examine its influence on the special lipid bilayer of the stratum corneum (SC). ATR-FTIR spectroscopic measurements were performed combined with tape stripping method on hairless mice in vivo. A SE containing gel was compared to another gel without SE. It was found that the preparations caused only minimal modifications in the lipid and the protein structure, promoting the skin hydration and therefore also the penetration of IBU. Although the degree of moisturization and penetration were more intense in the case of the SE containing gel treatment, it did not cause greater alterations in the SC structure than the gel without SE. It has been proven that SE acts as an effective and non-irritating hydration and penetration enhancer for IBU through skin.

Synthesis and spectroscopic and computational characterization of Zn4O(alicyclic or aromatic carboxylate)6 complexes as potential MOF precursors.

Potential metal-organic-framework precursors, Zn(4)O complexes with various alicyclic or aromatic carboxylate ligands, were prepared, in many cases quantitatively, from ZnO and the relevant carboxylic acids in the presence of trace amounts of water. The complexes obtained were characterized with various classical (titration) and instrumental (IR and NMR spectroscopies) methods and molecular modeling (PM3 and PM6 semiempirical quantum chemical methods and HF/6-31G** ab initio calculations). Structural peculiarities reflected in the success or failure in the synthesis could be rationalized with the combination of IR and NMR spectroscopies and molecular modeling.

[The nature of interactions between iron(III) and the structure of the Fe(III)-chitosan "complex"]. / A vas(III) es a kitozán közötti kölcsönhatás természete es a vas(III)-kitozán "komplex" szerkezete.

The interactions between the cationic polymer chitosan (a copolymer, consisting mainly of 2-amino-2-deoxy-D-glucopyranose and, to a lesser extent, of 2-acetamido-2-deoxy-D-glucopyranose, Chit) and iron(III) were investigated. The solution properties were studied by pH-metry, UV-Vis spectrophotometry and viscometry. Solid state iron(III)-Chit samples were also prepared and characterized by IR-spectroscopy and electronmicroscopy. In aqueous solutions, the precipitation pH of the FeO(OH) is significantly shifted towards the higher pH-s in presence of Chit. However, the additivity of the pH-metric titration curves, the lack of variation both in tin presence and absence of iron(III), indicate that there is no specific coordination chemical interaction between the Chit and ferric ions. It is well established that spherical FeO(OH) particles with afew nm diameter, morphologically similar to the core of the iron(III)-storage protein ferritin, are formed during the hydrolysis of iron(III) even in the absence of complexing agents. Such isolated FeO(OH) spheres were observed in samples obtained from solutions containing iron(III) and Chit. The fact, that visible precipitation of FeO(OH) can only be observed, when the Chit itself precipitates from aqueous solutions (i.e., pH approximately 7), indicates that the role of Chit in these systems is to inhibit the aggregation of the subcolloidal FeO(OH) particles. These observations are in strong contrast with those obtained for interactions between iron(III) and various anionic biopolymers, such as heparin, hyaluronate, dextran sulfate and chondroitin sulphate A and C, and suggest that coordination chemical interactions play very important role in determining the nanostructure of composite materials containing iron(III) and polysaccharides.

Study of the effect of stirring on foam formation from various aqueous acrylic dispersions.

Acrylic polymers in aqueous dispersions are very often used to prepare coating suspensions which contain insoluble particles. The mixing of the pigment suspension and the polymer dispersion is a very important step in the preparation of the liquid. The stirring can cause precipitation of the polymer and foam formation. Foam formation from different Eudragit dispersions was evaluated in this study. A high-speed mixer was applied and the foam and liquid phases formed were separated. The changes in concentration of the polymer in the two phases were studied by FT-IR with a horizontal attenuated total reflection (HATR) accessory. The presence of shape-holding foam can be detected at very different rates of stirring. The most intensive foam formation was detected for Eudragit FS 30 D. The Eudragit RL 30 D dispersion was the least sensitive to high-speed mixing. The relative content of the polymer in the foam was higher than that in the liquid. This is indicated by the accumulation of surface-active agent on the surface of the bubbles formed in the foam. This phenomenon differed considerably for the various dispersions. An exact knowledge of the foam formation from aqueous acrylic dispersions is very important in order to determine the parameters of mixing and the quantity of antifoaming agent.

Formation of spherical iron(III) oxyhydroxide nanoparticles sterically stabilized by chitosan in aqueous solutions.

The interactions between the cationic polymer chitosan (Chit) and iron(III) were investigated. The solution properties were studied by pH-metry, viscometry and dynamic light scattering. Solid state iron(III)-Chit samples were also prepared and characterized by IR spectroscopy and electron microscopy. In aqueous solutions, the precipitation pH of the iron(III) oxyhydroxide (FeOOH) is significantly shifted towards the higher pH values in the presence of Chit indicating that some interaction takes place between the iron(III) and the polymer. However, the additivity of the pH-metric titration curves, the lack of variation both in the viscometric and IR spectra of Chit in the presence and absence of iron(III), indicate the lack of direct complexation between the Chit and ferric ions. Isolated FeOOH nanospheres of 5-10 nm diameter were observed on the transmission electron microscopic pictures of samples obtained from solutions containing iron(III) and Chit, while from DLS measurements hydrodynamic units with a few hundred nm in diameter were identified. Our data support that Chit acts as steric stabilizer and inhibits the macroscopic aggregation of the subcolloidal FeOOH particles. Thus the iron(III)-Chit interactions offer a simple and economic way to fabricate nanometric size FeOOH spheres, morphologically similar to the core of iron(III)-storage protein, ferritin.