Modified MCM-41 as a drug delivery system for acetylsalicylic acid

The modification of prepared MCM-41 by different groups (amino, chloro and oxo) was studied. Prepared materials were treated by acetylsalicylic acid and hybrid materials were characterized, compared from the point of view of immobilized amount of active substance. The highest amount of acetylsalicylic acid was detected using methyl-tert- butyl ether as a solvent and MCM-41 without modification after 1 h (0.35 g per 1 g of the support) or MCM modified by amino group after 5 h (0.37 g per 1 g of the support) as a support. Using amino modified MCM, the longer treatment by acetylsalicylic acid converged to the equilibrium and after 24 h the immobilized amount was 0.3 g per 1 g. A dissolution in vitro study was carried out, comparing the stability of formed interactions. The slowest dissolution was detected using non-modified MCM-41 and oxo modified material.     

An investigation about the solid state thermal degradation of acetylsalicylic acid: polymer formation

An investigation about the thermal degradation of acetylsalicylic acid (ASA) is performed. It is verified that the thermal degradation of ASA produces not only salicylic acid (SA) and acetic acid (AA) as products but also an ASA polymer, which is transparent and solid. And also verified that the temperature in which the polymer is obtained influences its physical consistence (solid or semi-solid). Furthermore, the ASA polymer is very stable from a thermic point of view, as verified by TG and DSC analysis. X-ray diffraction patterns obtained for the ASA polymer show that it exhibits a low crystallinity.     

Tautomeric conjugate acids of 2-aminopyrroles: effect of substituents, solvation and cosolute

The tautomeric preferences of the conjugated acids of 2-aminopyrrole derivatives have been examined both in the gas phase and in aqueous solution by using a combination of quantum mechanical, self-consistent reaction field and Monte Carlo–free-energy perturbation methods. The results show that the nature of substituents, the solvent and the presence of cosolute are relevant factors in modulating the relative stability between the tautomeric conjugate acids protonated at the heterocyclic ring and at the exocyclic amino nitrogen. Thus, attachment of electron-withdrawing groups to the ring, solvation in polar solvents, and the presence of negatively charged cosolutes tend to favor protonation at the exocyclic amino nitrogen. Nevertheless, none of these factors alone suffice to change the tautomeric preference for the ring-protonated forms. The results point out that the concerted occurrence of the three factors is necessary to shift the tautomeric preference towards the conjugated species protonated at the exocyclic nitrogen.Contribution to the Jacopo Tomasi Honorary Issue     

Determination of acetylsalicylic acid by FIA-potentiometric system in drugs after on-line hydrolysis

A potentiometric flow injection (FI) system was developed for the acetylsalicylic acid (ASA) determination in drugs, without previous treatment. The tubular potentiometric electrode for salicylate (SA) was based on tricaprylyl-trimethyl-ammonium-salicylate (aliquat-salicylate) as the ion-exchanger, supported on poly(ethylene-co-vinyl-acetate) (EVA) matrix and applied directly onto a conducting support. The standards and samples were freshly prepared in ethanol solution (0.10 mol l(-1) Tris-SO(4) buffer, pH 8.0, containing 0.25 mol l(-1) Na(2)SO(4) and 8.0% v/v ethanol) to facilitate the dissolution of ASA and were injected directly into the system. The SA formed due to the on-line alkaline hydrolysis of alcoholic ASA solution, with 0.50 mol l(-1) NaOH (coil, 50 cm length), was monitored by the tubular electrode after neutralization with 0.25 mol l(-1) H(2)SO(4). A solution of 0.10 mol l(-1) Tris-SO(4) buffer (pH 8.0), containing 0.25 mol l(-1) Na(2)SO(4) was employed as carrier. In optimized conditions (flow rate of 2.1 ml min(-1) and volume of injection of 150 mul), the tubular electrode showed a linear response to ASA in the concentration range between 4.0x10(-3) and 4.0x10(-2) mol l(-1). A conversion factor of ASA to SA of 85% occurs in these conditions with an increase of about 130% in the signal to the system with on-line hydrolysis (three-channel) in comparison to the system without (one-channel). The response time of the electrode was about 5 s with an analytical frequency of 28 samples per h and a relative standard deviation (R.S.D.) of 2.1% for 30 successive injections. Determinations of ASA in tablet samples by the proposed method exhibited relative differences of 1.0-3.5%, compared to the official method of the British Pharmacopoeia. The useful lifetime of the sensor was greater than 1 month, in continuous use.     

The crystalline state of methylene blue: a zoo of hydrates

A re-investigation of the crystalline state of methylene blue has led to the identification of five different hydrates with clearly distinct structures. These include the already known pentahydrate, a hydrate with 2.2-2.3 equivalents of water, two dihydrates, and a monohydrate. Contrary to older reports, no trihydrate was found. The preparation and characterization of the hydrates as well as the transformations between them are reported. The applied analytical methods include X-ray powder diffraction (XRPD), infrared spectroscopy (ATR-IR), thermogravimetry (TGA), differential scanning calorimetry (DSC), dynamic water vapor sorption (DVS) and solution calorimetry (SolCal). A phase diagram of temperature vs. composition has been established, and the stability domains of the different hydrates as a function of water activity and temperature have been determined based on data from DSC, SolCal and suspension equilibration experiments. Four out of the five hydrates are thermodynamically stable within a certain range of temperature and humidity.     

Resorcin[6]arene as a building block for tubular crystalline state architectures

A resorcin[6]arene with an r-trans-cis-trans-cis-trans configuration of the pendant ethyl groups forms tubular crystal structures.     

Nanodisperse systems as transient state upon the formation of crystalline organometalsiloxanes

Properties of colloidal solutions formed in the course of hydrolytic condensation of phenyltrialkoxysilanes are studied upon the synthesis of organosiloxanolates of alkali metals and cage-like bimetallic organometalsiloxanes containing alkali and transition (Ni, Cu) or rare-earth (Eu) metals. Sizes and shapes of particles are determined by the dynamic and static light scattering methods. The aggregation stability of colloidal solutions is studied as a function of solvent nature and concentration of phenyltrialkoxysilane. Data obtained make it possible to suggest that disclosed aggregates are the nuclei of crystalline phase. Conditions of the existence of stable colloidal aggregates of sodium phenylsiloxanolate and Ni/Na-phenylsiloxane are determined. It is shown that, upon the dissolution of crystalline Ni/Na-phenylsiloxane in butanol, particles whose sizes are comparable with molecules of organometalsiloxanes are formed in the initial solution.     

The crystalline state as a dynamic system: IR microspectroscopy under electrochemical control for a [NiFe] hydrogenase

Controlled formation of catalytically-relevant states within crystals of complex metalloenzymes represents a significant challenge to structure–function studies. Here we show how electrochemical control over single crystals of [NiFe] hydrogenase 1 (Hyd1) from Escherichia coli makes it possible to navigate through the full array of active site states previously observed in solution. Electrochemical control is combined with synchrotron infrared microspectroscopy, which enables us to measure high signal-to-noise IR spectra in situ from a small area of crystal. The output reports on active site speciation via the vibrational stretching band positions of the endogenous CO and CN⁻ ligands at the hydrogenase active site. Variation of pH further demonstrates how equilibria between catalytically-relevant protonation states can be deliberately perturbed in the crystals, generating a map of electrochemical potential and pH conditions which lead to enrichment of specific states. Comparison of in crystallo redox titrations with measurements in solution or of electrode-immobilised Hyd1 confirms the integrity of the proton transfer and redox environment around the active site of the enzyme in crystals. Slowed proton-transfer equilibria in the hydrogenase in crystallo reveals transitions which are only usually observable by ultrafast methods in solution. This study therefore demonstrates the possibilities of electrochemical control over single metalloenzyme crystals in stabilising specific states for further study, and extends mechanistic understanding of proton transfer during the [NiFe] hydrogenase catalytic cycle.

Electrochemically-coupled IR microspectroscopy of single crystals provides insight into proton-coupled electron transfer in [NiFe] hydrogenase.     

Hydrogen-bonding effect on C NMR chemical shifts of amino acid residue carbonyl carbons of some peptides in the crystalline state

¹³C cross polarization-magic angle spinning NMR spectra were measured for a series of peptides containing -valine, -leucine and -aspartic acid residues, for which the crystal structures were already determined by X-ray diffraction, in order to investigate the relationship between hydrogen-bond lengths (R_N…O) and ¹³C chemical shifts of amide carbonyl carbons in the peptides. From these experimental results, it was found that the isotropic ¹³C chemical shifts (δ_iso) of the amino acid residues move linearly downfield with a decrease in R_N…O within the hydrogen-bonded length range considered here and also shown in our previous work on glycine and -alanine residues as expressed by δ_iso(ppm) = a − bR_N…O(Å) where a and b are 215.4 (ppm) and 14.2 (ppm Å⁻¹) for the -valine residue, 202.2 (ppm) and 10.0 (ppm Å⁻¹) for the -leucine residue, and 199.0 (ppm) and 9.6 (ppm Å⁻¹) for the -aspartic acid residue, respectively. Using these relations, the R_N…O values of some polypeptides in the crystalline state were determined through the observation of the amide carbonyl carbon chemical shifts. These values were compared with those determined by the X-ray diffraction method. Furthermore, quantum-chemical calculation of the ¹³C shielding constant for a model compound was carried out by the finite perturbation theory INDO method in order to ascertain the ¹³C shielding behavior in the formation of hydrogen bonds.     

Amphotericin B as a potential probe of the physical state of vesicle membranes

[structure: see text] The investigations described introduce a new role for a natural product such as amphotericin B as a potential biophysical reporter group to probe the physical state of a membrane. Specifically, we demonstrated that the K(+) efflux pattern reveals an interesting sterol dependence. This is suggested to be correlated to the physical state of the membrane showing high efflux in a vesicle membrane of intermediate fluidity.     

X-ray study on the effect of moisture on the crystalline state of cellulose

A method is presented for measuring the change of the intensity of x-ray diffraction peaks of cellulose specimens as a consequence of humidity changes of the specimens. Measurements performed showed a decrease of this intensity after drying pulp specimens initially kept in humid air. Thus the order in cellulose decreased during drying.     

The effect of physical state on the drug dissolution rate

In this work, the enhancement of drug dissolution rate through the preparation of new formulations containing Nimodipine in molecular level dispersion or in nanodispersion into poly(vinyl pyrrolidone) (PVP) matrix, was investigated. Differential scanning calorimetry (DSC) and modulated-temperature differential scanning calorimetry (MTDSC) in combination with X-ray powder diffractometry (XRPD) and scanning electron microscopy (SEM) studies showed that Nimodipine was amorphous in solid dispersions of 10 or 20 mass%, and mainly dispersed on a molecular level. This behaviour is attributed to the strong interactions taking place between the amine group of Nimodipine and carbonyl group of PVP. At higher drug loadings, crystal reflections in XRPD patterns and melting peaks of Nimodipine in DSC traces, indicated presence of drug in crystalline form. Micro-Raman studies in combination with SEM micrographs showed that the mean particle size increases with drug content in the formulations, up to 10 μm. Moreover, both XRPD patterns and micro-Raman spectra seem to indicate that Nimodipine crystallized in a second, thermodynamically stable, crystal modification II. The physicochemical characteristics of Nimodipine and the particle size distribution directly affect the dissolution rate enhancement, which is higher in amorphous dispersions.     

Characterization of an oxaluric acid derivative as a guanine oxidation product

The oxidation of guanine in the dinucleoside monophosphate d(GpT) by an oxo-metalloporphyrin generates a linear oxaluric acid derivative after heating at 65 degrees C for 30 min and at neutral pH.     

Characterization of the ladder polymerization of a crystalline cyclotetradiyne monomer

The polymerization of the cyclic tetradiyne monomer, [? (CH₂) ₂? C?C? C?C? (CH₂)₂? ]₄, containing interstitial chloroform has been investigated using Raman and Fourier-transform infrared spectroscopy and x-ray diffraction techniques. A loss of crystallographic register between chains occurs during the polymerization reaction, although crystalline order in the chain-axis projection is retained. These studies indicate that 50 Mrad of ⁶⁰Co γ-ray irradiation produces 1,4-addition polymerization at most of the diacetylene functionalities. Unreacted diacetylene groups are present primarily, although not completely, in soluble oligomeric material. Infrared spectroscopy indicates that this low molecular weight material has a butatriene (cumulene) backbone structure rather than the acetylenic structure of the insoluble polymer.     

Enzymatically prepared n-alkyl esters of glucuronic acid: the effect of freeze-drying conditions and hydrophobic chain length on thermal behavior

In this work, some of the physicochemical properties of enzymatically prepared n-alkyl esters of glucuronic acid are presented. Two questions are addressed. The first concerns the influence of post-purification freeze-drying conditions on octyl glucuronate thermotropic behavior. Depending on the amount of water added before freeze-drying, the alpha/beta anomeric ratio determined by (1)H NMR is affected and differences are observed in DSC thermograms probably due to polymorphism. The second question concerns the effect of hydrophobic chain length on the thermal behavior. An increase of both transition temperature and transition enthalpy is observed by increasing the number of carbon atoms in the alkyl chain (C8相似文献   

Characterization of bupivacaine-loaded formulations based on liquid crystalline phases and microemulsions: the effect of lipid composition

This report details the structural characterization and the in vitro drug-release properties of different local anesthetic bupivacaine (BUP)-loaded inverted-type liquid crystalline phases and microemulsions. The effects of variations in the lipid composition and/or BUP concentration on the self-assembled nanostructures were investigated in the presence of the commercial distilled glycerol monooleate Myverol 18-99K (GMO) and medium-chain triglycerides (MCT). Synchrotron small-angle X-ray scattering (SAXS) and rotating dialysis cell model were used to characterize the BUP formulations and to investigate the in vitro BUP release profiles, respectively. The evaluation of SAXS data for the BUP-loaded GMO/MCT formulations indicates the structural transition of inverted-type bicontinuous cubic phase of the symmetry Pn3m → inverted-type hexagonal (H(2)) phase → inverted-type microemulsion (L(2)) with increasing MCT content (0-40 wt %). In the absence of MCT, the solubilization of BUP induces the transition of Pn3m → H(2) at pH 7.4; whereas a transition of Pn3m → (Pn3m + H(2)) is detected as the hydration is achieved at pH 6.0. To mimic the drug release and transport from in situ formed self-assembled systems after subcutaneous administration, the release experiments were performed by injecting low viscous stimulus-responsive precursors to a buffer in the dialysis cell leaving the surface area between the self-assembled system and the release medium variable. Our results suggest that the pH-dependent variations in the lipidic partition coefficient, K(l/w), between the liquid crystalline nanostructures and the surrounding buffer solution are significantly affecting BUP release rates. Thus, a first step toward understanding of the drug-release mechanism of this drug-delivery class has been undertaken tackling the influence of drug ionization as well as the type of the self-assembled nanostructure and its release kinetics under pharmaceutically relevant conditions.     

Simultaneous determination of acetylsalicylic acid and salicylic acid by gas-liquid chromatography using a new methylation technique

Summary A GLC method of simultaneous determination of acetylsalicylic acid and salicylic acid after a simple and elegant methylation is presented. Acetonic solution of these acids is refluxed with methyl iodide and potassium carbonate for 30 minutes and then gas chromatographed with a column of 3% OV 17 on Varaport 30, 70–80 mesh, AW/DMCS. The methylation is quantitative in 0.001–0.1 M solutions. The detection limit is about 25 ng.