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Recent scientific publications have already demonstrated that co-grinding appears as an efficient, solvent-free technique for preparing cyclodextrin complexes and improving physicochemical properties of active ingredients. The improvement of solubility and dissolution rate could enhance the biopharmaceutical properties of the active ingredients in solid pharmaceutical products. Furthermore stable, amorphous, organic solvent-free inclusion complexes could be formed efficiently in the industrial environment. In this study terbinafine hydrochloride (TER), an antifungal BCS II drug was chosen as a model drug. The aim of this study was the follow-through of inclusion complex preparation by co-grinding using several analytical methods. TER and amorphous cyclodextrin derivatives (hydroxypropyl-β-cyclodextrin; heptakis(2,6-di-O-methyl)-β-cyclodextrin) were used for the preparation of products. The thermoanalytical behavior was analyzed by differential scanning calorimetry (DSC), the occurred changes in crystalline properties were investigated by X-ray powder diffractometry (XRPD) and hot-humidity stage X-ray powder diffractometry (HOT-XRPD). Chemical interactions between the components were analyzed by Raman spectroscopy and Fourier transform infrared spectroscopy (FT-IR). Dissolution studies of TER and products were also carried out. Cyclodextrin-TER complexes were prepared in the 1:1 molar ratio. DSC and XRPD studies suggested that the crystallinity of products gradually decreased by the increasing grinding time, and after 75 minutes of co-grinding the products were completely amorphous. HOT-XRPD studies revealed that the amorphous product containing hydroxypropyl-β-cyclodextrin did not change with increasing temperature. However, in the same process, the heptakis(2,6-di-O-methyl)-β-cyclodextrin containing product recrystallized in a new crystalline phase. Raman and FT-IR spectroscopy confirmed the molecular interactions between the components. Dissolution studies showed that the dissolution rate of complexes improved, and the solubility of TER increased both in simulated gastric and intestinal fluid, depending on the pH of the dissolution medium.

The steps of formation of an inclusion complex produced by the co-grinding of gemfibrozil and dimethyl-β-cyclodextrin were investigated by differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD) and Fourier transform infrared (FTIR) spectroscopy with curve-fitting analysis. The endothermic peak at 59.25 °C reflecting the melting of gemfibrozil progressively disappeared from the DSC curves of the products on increase of the duration of co-grinding. The crystallinity of the samples too gradually decreased, and after 35 min of co-grinding the product was totally amorphous. Up to this co-grinding time, XRPD and FTIR investigations indicated a linear correlation between the cyclodextrin complexation and the co-grinding time. After co-grinding for 30 min, the ratio of complex formation did not increase. These studies demonstrated that co-grinding is a suitable method for the complexation of gemfibrozil with dimethyl-β-cyclodextrin. XRPD analysis revealed the amorphous state of the gemfibrozil–dimethyl-β-cyclodextrin product. FTIR spectroscopy with curve-fitting analysis may be useful as a semiquantitative analytical method for discriminating the molecular and amorphous states of gemfibrozil.

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 aim of this study was to evaluate the interaction between the film-forming sodium alginate and lactose monohydrate. This combination is used in the co-spray-drying technique for microencapsulation, but no respect on the structure of the film formed has not been published previously. From mechanical tests, positronium lifetime measurements and FT-IR studies on free films containing different ratios of film-former and lactose, we concluded that the mechanical strength of the sodium alginate film decreased with the increasing proportion of lactose. The free volume in the polymer matrix decreased to a minimum as the lactose content was progressively increased to 40%, but subsequently increased at higher lactose contents. The explanation of this phenomenon is the filling of the holes with the sugar. As lactose became predominant component, the structure of the polymer network weakened. These conclusions were supported by the FT-IR findings. The present results permit a clear explanation of the previously reported favourable effects of this film-forming combination on the dissolution of the active agent from the microcapsules.

A tricyclic, piperidine derivative of antihistamines, loratadine, which belongs in class II of the Biopharmaceutical Classification System, was investigated. It is an ionizable drug, whose solubility depends on the gastrointestinal pH, and the bioavailability is therefore very variable. The aim of this work was to enhance the dissolution and make the solubility of loratadine independent of pH. Inclusion complexes were prepared between loratadine and dimethyl-β-cyclodextrin in two different molar ratios by three techniques (physical mixing, kneading and spray-drying). The formation and physicochemical properties of the inclusion complexes were investigated by means of dissolution tests, thermal analysis and Fourier Transform Infrared spectroscopy. The instrumental examinations proved the presence of partial or total complexes depending on the preparation method and molar ratio, which resulted in better dissolution. For some compositions and preparation methods, the application of this cyclodextrin made the solubility of loratadine independent of pH.

The majority of active pharmaceutical ingredients are poorly soluble in water. The rate-determining step of absorption is the dissolution of these drugs. Inclusion complexation with cyclodextrin derivatives can lead to improved aqueous solubility and bioavailability of pharmacons due to the formation of co-crystals through hydrogen-bonding between the components. Inclusion complexes of loratadine were prepared by a convenient new method involving microwave irradiation and the products were compared with those of a conventional preparation method. Dissolution studies demonstrated that the solubility and rate of dissolution of loratadine increased in both of the methods used. The interactions between the components were investigated by thermal analysis and Fourier Transform Infrared studies. The microwave treatment did not cause any chemical changes in the loratadine molecule.

The Zn 4 O(RCO 2 ) 6 complexes of a selection of straight- and branched-chain carboxylic acids have been prepared in CCl 4 and characterized by their 13 C NMR, 1 H NMR and mid-FT-IR spectra. Their structural stability was studied by FT-IR-spectroscopy over a 4-day long period of time in CCl 4 solution and as cast films. The observed characteristic spectroscopic features have been discussed. The cast film samples showed extremely diverse behaviour from instant decomposition to the perfect conservation of the original T d symmetry, even though water was not excluded from the system. An explanation, supported by ab initio quantum chemical calculations on the conformation of the free carboxylate ions with various alkyl-chains, has been given for the diverse behaviour of the samples. Formation of a hydrocarbon moiety, with somewhat extended anti-periplanar (all- trans ) conformation, perpendicular to the carboxylate plane was the essential factor in the preservation of the structure and the quaternary α-carbon was an additional requirement to sustain its symmetry. Two attempts at preparing the corresponding Zn 4 O(RCO 2 ) 6 complexes from water have been successful in the cases when the R-groups fulfilled the requirements in geometry stated above.

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.

The permeable polymer film-formation behavior of a Eudragit RS dispersion was investigated in response to stirring at various rates and for various times in an Ultra Turrax instrument. No additives were used. The minimum film-forming temperature of the liquid, the thermal behavior of the film and the compositions of the dispersion and the foam arising were investigated. It was found that, at a given mixing time, shape-retaining foam formation could be detected at over 17,500 rpm. The polymer was enriched in the foam, while its quantity was decreased in the liquid. The minimum film-forming temperature of the liquid phase did not vary significantly, with the exception of the rate of 24,000 rpm, when a uniform film was not formed because of the bubbles. The glass-transition temperatures of the films formed did not exhibit any differences. Film formation was not influenced by the stirring time at a given rate. It was found that the efficiency of homogenization should not be increased by using a high stirring rate, as a uniform, smooth film did not develop, such a film being indispensable to ensure appropriate drug release. Copyright © 2006 John Wiley & Sons, Ltd.

Inclusion complexation between dimethyl-β-cyclodextrin and a very poorly water-soluble serum lipid-regulating agent, gemfibrozil, was studied. Products were prepared by several methods (physical mixing, kneading, spray-drying and ultrasonic treatment) in four different molecular ratios (2:1, 1:1, 1:2 and 1:3). The possibility of complex formation between the drug and the host molecule was studied by thermal analysis. Supplementary techniques, such as Fourier transformation-infrared spectroscopy and X-ray diffractometry, were also applied to interpret the results of thermal study of the products.

Inclusion complexation between cyclodextrin derivatives (hydroxypropyl-β-cyclodextrin and methyl-β-cyclodextrin) and a very poorly water-soluble antifungal agent, ketoconazole, was studied. Solid products were prepared by physical mixing, kneading and spray-drying methods in four molecular ratios: 2:1, 1:1, 1:2 and 1:3. The possibility of complex formation between the drug and the cyclodextrins was studied by thermal analysis. Supplementary techniques, such as X-ray diffractometry and Fourier transformation-infrared spectroscopy, were also applied to interpret the results of the thermal study of the products.

Twenty-two samples of zinc carboxylates were prepared from saturated, non-cyclic carboxylic acids with systematically altered hydrocarbon chain structures under well-defined conditions. Essential temperature- and solvent-induced changes concerning the coordination of the carboxylate group are shown using selected prepared samples, and general rules for systems containing zinc carboxylates in nonpolar media are presented. It is shown that there are three possible structural forms for zinc carboxylates: polymeric sheet, polymeric chain, and closed tetranuclear oxo complex molecules. These forms are closely related through their physical and chemical transitions. The results show that the spatial structure of the hydrocarbon chain is a crucial factor, besides physical and chemical conditions, limiting the possible forms of zinc carboxylates present in the system. The principles presented enable us to predict and design the behaviour of a system containing zinc carboxylate additives.

Polymer-supported oxidic osmium catalysts based on cross-linked poly(4-vinyl pyridine) were synthesized by various routes and characterized by a number of physical techniques (Raman, IR, XPS, 13 C and 15 N solid-state NMR spectroscopy). Model compounds of type Os 2 O 6 L 4 (L = pyridine, 4- iso -propyl pyridine, and 4- tert -butyl pyridine) were obtained under the conditions of the catalyst synthesis. The catalytic systems were successful in the dihydroxylation of alkenes.

The compositions of paraffinic deposits obtained from oil wells and pipelines were studied. It was established that, besides the well-known asphaltene, malthene, resin and paraffin, a hydrophobic paraffin derivative (solid hydrophobic fraction) of higher molar mass and melting point, containing polar end-groups (CO and COO−), can also be isolated. X-ray analyses showed this material to be an organocolloid of lamellar structure. Small angle X-ray scattering measurements demonstrated that the substance readily swells in toluene. When its solutions and its suspensions prepared by cooling are studied in aromatic aliphatic solvent mixtures, they exhibit a great variety of structural characteristics. Optical measurements indicate that its tendency to aggregate is very sensitively affected by the polarity of the hydrocarbon mixture, and by temperature. Its presence at a concentration of 1–2% stabilizes water-in-oil emulsions, which is explained by changes in the colloidal state of the paraffin derivative.

A study was launched to clarify the influence of the spatial structure of the alkyl chain on the products of the direct neutralization reactions between zinc hydroxide and several non-cyclic saturated carboxylic acids in the presence of an excess of either the carboxylic acid or zinc hydroxide. The species formed were identified on the basis of their FT-IR spectra in the mid-IR region. Straight-chain acids produced the corresponding zinc bis-carboxylates with polymeric sheet structure under all circumstances. The species present in the products of the branched-chain carboxylic acids depended strongly on the nature of the component in excess and the bulk of the alkyl group. Besides the starting materials the reaction mixtures contained two carboxylate species in various ratios. One of them was the zinc bis-carboxylate of the branched-chain carboxylic acid, characterized by an additional v CO band at around 1630 cm −1 , above the usual two strong carboxylate stretching bands. The other species was the corresponding complex Zn 4 O(RCOO) 6 . The conditions of foundation of these three forms of zinc carboxylates were formulated on the basis of the decreasing possibility of interaction between the neighbouring alkyl chains to form a polyethylene subcell in the sequence of: Zn(RCOO) 2 (polymeric sheet) > Zn(RCOO) 2 (intermediate form) > Zn 4 O(RCOO) 6 (tetranuclear complex).

The temperature-induced formation of an intermediate modification (the precursor of the tetranuclear oxo complex) of straight-chain zinc carboxylates (even numbered between C6 and C18) was studied by means of temperature-dependent Fourier transform infrared spectroscopy and differential scanning calorimetry. The formation of this intermediate modification required only low interaction between the alkyl chains, which could be caused by temperature, solvent or geometric incompatibility. The infrared spectra proved that rearrangement of the carboxylate groups and destruction of the all-trans arrangement of the alkyl chains occurred simultaneously during the solid-liquid transition of the samples. A simple linear model was employed to interpret the measured enthalpies and the calculated entropies. The enthalpy contributions of the alkyl chains predominated in the transitions between the different modifications and in the formation of the polymeric sheet structure of the straight-chain zinc carboxylates.

The complex [Zn 4 O(OOCC(CH 3 ) 3 ) 6 ] contains a tetrahedral oxo-centred metal cluster unit. Structures of this type have been characterised by X-ray diffraction, and in some cases exact tetrahedral symmetry has been found. However, crystal structures of high symmetry can conceal molecular structures of lower symmetry, averaged by static or dynamic disorder. The symmetry of this complex has therefore been checked over a short time-frame, in solution, by using vibrational spectroscopy with isotopic substitution. The antisymmetric vibration of the central oxide ion ( t 2 symmetry in the T d point group) has been located unambiguously and shown to be free of splitting by any symmetry lowering, and moreover to be essentially purely localised about the central oxygen.