HII mesophase and peptide cell-penetrating enhancers for improved transdermal delivery of sodium diclofenac

This study develops a novel transdermal delivery vehicle for the enhanced delivery of sodium diclofenac (Na-DFC). The system utilizes the advantages of reversed hexagonal lyotropic liquid crystals (H_IILC), combined with a peptide cell penetration enhancer (CPE), creating together an adaptable system that provides versatile options in the field of transdermal delivery.This enhancer peptide is based on a family of amphipatic peptides that exhibit improved membrane permeability. Franz permeation cell experiments revealed that the peptide enhancer (RALA) improved Na-DFC skin penetration of the liquid crystal 2.2-fold.We studied the structural effects of RALA solubilization on the H_II mesophase. RALA acts as a chaotropic agent, interfering in the structure of the water, and causes a measurable swelling of the aqueous cylinders by 5 Å.Small angle X-ray scattering (SAXS) and attenuated total reflectance–Fourier transform infrared (ATR–FTIR) measurements reveal enhanced hydration of the glycerol monooleate (GMO) headgroups and a 6.5% increase in the fraction of non-freezable water resulting from RALA incorporation. RALA caused a gradual increase in the GMO effective headgroup area due to the hydration, leading eventually to a transform of the hexagonal structure towards a lamellar one. Circular dichroism and ATR–FTIR measurements showed a conservation of the peptide structure when incorporated into the H_II mesophase.The combined H_IILC-CPE systems can serve as high potential vehicles for a variety of drugs, as they can easily be modified by varying the composition and temperature, according to the required dose and delivery features.     

Thermal behaviour of diclofenac, diclofenac sodium and sodium bicarbonate compositions

This work aims to investigate the thermal behaviour of diclofenac, diclofenac sodium, and NaHCO₃ both as single components and binary mixtures. In particular, the melting point and latent heat of fusion binary diagrams of the diclofenac sodium/diclofenac mixtures at different mole fraction compositions were investigated in order to gain information about the thermal behaviour of their solid mixtures. A good agreement between liquidus curves, calculated by the Schroeder-Van Laar equation from fusion enthalpies and temperatures, and the experimental results was found. For all binary compositions, an endothermic effect at 153°C, probably due to the eutectic fusion, is present.     

Complementary C3-symmetric donor-acceptor components: cocrystal structure and control of mesophase stability

The overlap of pi-complementary planar organic frameworks is used to direct the assembly of extended columns of alternating donor and acceptor units. The electron-rich partner, hexaalkoxytriphenylene, is a familiar mesogen, while the electron-accepting complement is mellitic triimide, a new C(3)-symmetric building block that may be readily alkylated at its periphery without compromising its electron-accepting ability. A cocrystal of examples of the two components demonstrates pi-facial overlap of the complementary aromatic surfaces. Preparation of a series of alkylated derivatives of each component allowed the study of an array of 1:1 stoichiometry mixtures. For the optimum donor-acceptor organized mesophases within this grid, temperature stability ranges of well over 100 degrees C are observed, some of which extend below room temperature. X-ray analysis confirms the formation of hexagonally packed, alternating, donor-acceptor columns within each of the observed mesophases. The dramatic effect on mesophase formation and stability engendered via donor-acceptor organization within discrete columns is discussed in terms of the interplay of forces leading to mesophase formation, and the potential to tune mesophase characteristics via manipulation of these factors.     

毛细管电泳测定双氯芬酸钠制剂中的双氯芬酸钠

建立了制剂中双氯芬酸钠毛细管电泳高频电导分析法,并用于氯芬黄敏片及双氯芬酸钠肠溶片中双氯芬酸钠的测定。对电泳介质的种类、浓度以及操作电压和进样量等影响因素进行了优化。实验采用5mmol/L乳酸为缓冲溶液,22.0kV为分离电压,可在9min内实现对双氯芬酸钠的分离检测。在最佳实验条件下,双氯芬酸钠的线性范围为0.4~100μg/mL,检出限为0.1μg/mL。成功地检测了氯芬黄敏片及双氯芬酸钠肠溶片的有效成分双氯芬酸钠,回收率为92.4%~103.0%。     

Phase behaviour of blends with mesophase components

Temperature transitions and structural transformations were studied for blends of two thermotropic mesophase cyclolinear polymethylsiloxanes with linear PDMS of various molecular weights by means of DSC, optical polarizing microscopy, and optical interferometry. Compatibility of the components which depends on the chemical structure of cyclolinear polymethylsiloxanes, molecular weight of PDMS, composition, and temperature affect formation of mesophase in cyclolinear polymethylsiloxanes. The most interesting aspect of the phase behaviour consists in the fact that it is possible to reach compatibility of the components in the mesomorphic state for the blends of two cyclolinear polymethylsiloxanens due to various annealing regimes in one‐phase molten state.     

In vitro percutaneous transport of sodium diclofenac and diclofenac from oleaginous vehicle

The penetration enhancement of sodium diclofenac and diclofenac by alcohols with various alkyl chains (C8 to C14) was evaluated by the steady state flux of diclofenac through rat abdominal skin. Decanol showed the greatest effect in this series. A more remarkable enhancing effect of the alcohols was observed in sodium diclofenac than in diclofenac. Diclofenac can penetrate through the ethylene-vinyl acetate membrane as a lipoid model membrane, but sodium diclofenac can not. Decanol enhanced the penetration of phenol red being dependent on its concentration in the vehicle. Therefore, decanol may interact with lipoid components of the skin and increase the aqueous pathway in the skin. These results indicate that sodium diclofenac and diclofenac may be penetrated through partially different pathways.     

Effect of temperature on solvation behaviour of diclofenac sodium salt in aqueous glycine and l-proline solutions

Apparent molar volume (V_2,ϕ) and apparent molar isentropic compressibility (K_s,2,ϕ) of diclofenac sodium salt (DSS) drug within the concentration range of (0.001 to 0.008) mol · kg⁻¹ in (0.01, 0.03 and 0.05) mol · kg⁻¹ aqueous glycine and l-proline solutions are computed from the experimental density (ρ) and speed of sound (u) values at T = (293.15 to 313.15) K and atmospheric pressure. Derived parameters such as partial molar properties, transfer partial molar properties, hydration numbers and Hepler’s constant are computed from the data of V_2,ϕ and K_s,2,ϕ. These parameters have been used to understand the effect of temperature on interactions between DSS drug and aqueous glycine/l-proline solution. Furthermore, the structure making and breaking ability of DSS drug in probed solutions are analysed at experimental conditions.     

Indirect fluorometric determination of diclofenac sodium.

A simple and easy method of analysis for diclofenac sodium is reported. A spectrofluorometric method for the microdetermination of diclofenac sodium has been developed through its reaction with cerium(IV) in an acidic solution and measurement of the fluorescence of the Ce(III) ions produced. Under the optimum experimental conditions for the oxidation reaction, 1.0 M H2SO4 with 90 min of heating time (100 degrees C), the range of application is 124.3-600 ng mL(-1) and the limit of detection is 72.7 ng mL(-1). The proposed method was applied to the determination of diclofenac sodium in pharmaceutical tablets. The results of the analysis show a good agreement with those obtained by the official USP 27 HPLC method.     

Thermal behaviour of diclofenac sodium: decomposition and melting characteristics

The thermal behaviour and melting characteristics of diclofenac sodium were investigated using various instrumental techniques--differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared (FT-IR) spectroscopy and thin layer chromatography (TLC). DSC analysis of diclofenac sodium performed under dynamic flow of either synthetic air or helium or nitrogen did not produce any sharp endothermic peak characteristic of melting peak of a pure substance. Both the rate of scanning of the sample and the environmental atmospheric condition significantly affected the thermographic profile of diclofenac sodium. An exothermic peak prior to an endothermic peak corresponding to melting of the substance appeared when heated under dynamic flow of synthetic air suggesting oxidation (decomposition) of diclofenac sodium before reaching its melting point. In fact, at a scanning rate of 1 degree C/min only the exothermic peak appeared in the thermogram, suggesting complete decomposition prior to melting under the dynamic flow of synthetic air. DSC, FT-IR and TLC data obtained from samples heated under the dynamic flow of either helium or nitrogen revealed formation of a related compound, 1-(2,6-dichlorophenyl)-indolin-2-one, an indol-cyclic amide, as a result of an intramolecular cyclization reaction during the heating process. TGA data demonstrated a loss of 11.4-20.2% of the mass of diclofenac sodium when heated under various environmental conditions, and also supported the oxidative nature of degraded product(s) when the thermal process occurred slowly under a dynamic flow of synthetic air.     

Evolution of the structure of mesophase polyfluoroalk-oxyphosphazenes and liquid crystalline copolyesters

Comparative analysis of the temperature evolution of the structure of linear organoelement polyfluoroalkoxyphosphazenes and wholly aromatic main-chain copolyesters was carried out using X-ray analysis, differential scanning calorimetry and dynamic mechanical testing within a wide temperature range. Experimental observations show that flexible-chain polyfluoroalkoxyphosphazenes are inclined to formation of the columnar mesophase and condis crystalline structures, while rigid-chain random copolyesters mainly exhibit peculiar smectic and nematic liquid crystalline states.     

Spin probes in structure studies of petroleum mesophase pitch

The ESR spectra of petroleum pitch labeled with the stable copper-porphyrin complex and changes in the spectra due to pyrolysis are analyzed. It is concluded that the functions of carriers and traps for unpaired electrons in mesophase pitch are performed by anisotropic associates or crystallites sized about 2.0 nm. The intermodular interactions between the parallel layers of anisotropic associates may be significant. They increase when the molecular associates pass to the paramagnetic state and determine the preferable packing of the paramagnetic crystallites one over another. Translated fromZhurnal Strukturnoi Khimii, Vol. 38, No. 5, pp. 902–907, September-October, 1997.     

Structure and properties of the mesophase of syndiotactic polystyrene. I. Effect of casting conditions on the preparation of the mesophase

A syndiotactic polystyrene–toluene solution was cast under two different casting conditions to obtain the δ form. A systematic study of its conformational transition, thermal behavior, and structural transformation as functions of the annealing temperature and time was performed. Spectroscopic studies revealed the content of its helical conformations and its retention up to 190 °C. Thermal analyses showed a significant difference in the transformation from the γ form to the α form. The retention of the intermediate emptied clathrate form (mesophase) of the conformational order for a longer duration (from 120 to 180 °C) in a syndiotactic polystyrene membrane cast at room temperature was confirmed by X‐ray diffraction analysis. On the basis of the experimental results in this work, the transition mechanism is discussed. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 530–536, 2002; DOI 10.1002/polb.10120     

Thermodynamics of sodium diclofenac salt aqueous solutions at various temperatures

Enthalpies of solution and dilution of aqueous solutions of sodium diclofenac salt were measured by isoperibolic calorimeter at 293.15, 298.15, 303.15, 308.15 and 318.15 K. The concentration of the electrolyte was restricted to solubility salt at various temperatures and did not exceed 0.035–0.057 mol kg⁻¹ values depending on the studied temperature. The virial coefficients were derived from Pitzer’s model and the excess thermodynamic functions of both the solution and the components of the solution were calculated. The analysis of thermodynamic characteristics of the solution from concentration and temperatures was carried out and discussed.     

Structure and properties of the mesophase of syndiotactic polystyrene. II. Effect of stepwise extraction on the preparation of the mesophase

In this study, a novel stepwise extraction method has been examined. The guest molecules housed between the helices of the clathrate δ form of syndiotactic polystyrene can be removed completely with this method. A systematic study of the preparation of a solvent‐free mesophase (emptied clathrate) membrane, its helical and residual solvent contents, and its structural transformations has been performed. In this first attempt, an enhancement in the TTGG helical content has been observed in the extracted membrane, and a conceptual mechanism is proposed. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 269–273, 2003     

The thermotropic mesophase structure of two long-chain alkyl pyridinium halides

The thermotropic phase transitions and the mesophase structure of two long-chain alkyl pyridinium halides are described. From small angle X-ray diffraction, optical microscopy, differential scanning calorimetry and dilatometry, the single liquid-crystalline phase found in each material is identified as smectic A. It is argued that the molecules within a layer are oriented alternately and packed in an interdigitated fashion, with the anions sandwiched between the pyridinium rings.     

NMR study on the low-affinity interaction of human serum albumin with diclofenac sodium

The low-affinity interaction between human serum albumin (HSA) and Diclofenac sodium (DCF) was studied using NMR techniques. Both 13C-NMR chemical shift and linewidth show that the dichlorophenyl ring in DCF molecule plays a primary role in its interaction with HSA. Langmuir adsorption isotherm was applied to evaluate the association constant K and the number of binding sites n of the drug/HSA complex through (1)H-NMR spin-lattice relaxation measurement. The results indicate that Langmuir isotherm can perfectly explain the capacity of low-affinity binding of proteins for the ligands.     

New mesomorphic organocyclosiloxanes II. Thermal behaviour and mesophase structure of organocyclohexasiloxanes

Investigations of thermotropic phase transitions performed on organocyclosiloxanes [PhSi(O)OSiR]₆, where R is Me₃, Me₂(CH₂Cl) or Me₂(CH≃CH₂), have revealed that all these hexamers are mesomorphic compounds. The hexamers exhibit uncommon polymesomorphic behaviour forming two quite different mesomorphic structures. The molecular arrangement in the low temperature (LT) modification is characterized by two-dimensional (2D) long-range order with hexagonal packing. The X-ray diffraction pattern and peculiarities of molecular packing in the crystal lead us to suggest that the LT-mesophase is columnar, presumably of the Col_hd type. The LT-mesophase is formed by dimeric moieties, which associate with each other in column-like substructures, the ring planes not orthogonal to the stack axis. The high temperature (HT) mesophase is a plastic crystal (3D-order), where molecules take up positions in a face-centred cubic lattice. This is a very uncommon example of thermal behaviour for plastic crystals that provides a unique opportunity to bridge the gap between plastic crystalline and liquid crystalline mesomorphic behaviour. The thermal and structural properties of the mesophases depend upon the type of side groups of the hexamers. The size of the ring also affects the phase behaviour and the mesomorphic structure. This conclusion is consistent with data obtained by us earlier for cyclotetrasiloxanes.     

The structure and morphology of some mesophase polymers with flexible and stiff macromolecules

Comparative analysis of the temperature behavior and phase composition of linear flexible-chain polyfluoroalkoxyphosphazene and linear stiff-chain copolyester was carried out using X-ray diffraction at elevated temperatures and DSC measurements. The main idea of the study was to examine the nature of noncrystalline phases of such mesomorphic materials and to identify their structure and specific features of the morphology. The data obtained show that both flexible-and stiff-chain polymers despite the fact, whether their macromolecules contain or not contain mesogenic groups, are able to form columnar mesophases, whereas the formation of typically LC nematic and smectic states is the inherent structural feature only of stiff-chain polymeric systems, which exhibit peculiar aperiodic layer structures.