Optimization of preparation of matrix pellets containing ethylcellulose

The aim of this study was to investigate the effects of the parameters of the spheronization and the nature of the wetting liquid on the properties of matrix pellets prepared by extrusion and spheronization. Ethylcellulose was used as a matrix former, microcrystalline cellulose as a filler, atenolol as a model active agent, and water and a water–ethanol mixture as liquids. The formation of the pellets and the interactions of the components were evaluated via mechanical, dissolution and morphological studies on the pellets. A factorial design was used to determine the effects of the evaluated factors. It was concluded that significant effects were exerted not only by the operational parameters, but also by the nature of the liquid. The breaking hardness and the dissolution revealed that the ethanol in the liquid caused changes in the wettability of the components and consequently in the matrix structure. This was explained by a comparison of the relative importance of the factors. The alterations induced by ethanol were preferable in the dissolution, because the possibility of the burst effect in the first phase of dissolution can then be avoided. However, it is not favourable as concerns the sphericity and the mechanical properties of the pellets.     

Restricted dissolution and derivatization capacities of cellulose fibres under uniaxial elongational stress

Cellulose is a future major source of materials and biofuel but its extraction and its chemical or enzymatic treatments are difficult, polluting and inefficient tasks. The accessibility of the reagents to cellulose chains is indeed limited. Classical evocated reasons for this lack of accessibility are pore structure, tight hydrogen bond arrays, crystallinity and presence of resistant materials like lignin. Studying dissolution of cotton hairs and regenerated cellulose fibres in various solvents under uniaxial tension, we found that tension is preventing these fibres to dissolve in chemicals that would dissolve the same cellulose fibres tension-free. We show that what is controlling dissolution is not the degree of swelling since, at the same degree of swelling, fibres under tension do not dissolve while fibres without tension do. An important result is that when a fibre under tension (thus swollen but not dissolved) is breaking, it is immediately dissolving. Under tension, when the solvent is present around cellulose chains, it is activated to solvate the chains only when tension stress is released. A chemical reaction like acetylation of cellulose fibre under tension also gives an interesting result. The degree of substitution remains very low while the same experiment performed without tension leads to higher degree of substitution followed by the dissolution of the fibre (even increasing further the DS due to homogeneous reaction). We postulate that the lack of dissolution capacity or reacting activity under tension can be due to the hampering of local conformational movements, cellulose chains being not able to perform axial movements. The availability of performing local conformational movements could be a main component of cellulose activation.     

Particle size reduction for improvement of oral absorption of the poorly soluble drug UG558 in rats during early development

Background: The exposure of UG558 was not good enough using traditional microsuspensions. Aim: The aim of this study was to find out whether nanosuspensions were a better choice compared with a microsuspension, for an acidic substance with a water solubility in the order of 2 μM (pH 6.8, small intestinal pH) and no permeability limitations. Methods: UG558 was ground by a planetary ball mill. The particle size was measured by laser diffraction and the stability of the particle sizes was followed. The pharmacokinetic parameters of UG558 administered as nanosuspension have been compared with those from microsuspension using rat as in vivo specie. Both formulations were administered orally. The nanosuspension was also administered intravenously. Results: The particle size of the nanosuspensions was about 190 nm and about 12 μm for the microsuspensions. At the administered doses, solutions were no alternative (e.g. due to limited solubility). Already at the lowest dose, 5 μmol/kg (5 ml/kg), a significant difference was observed between the two suspensions. These results were further confirmed at a high dose (500 μmol/kg, 5 mL/kg). Thus, the study demonstrated a clear correlation between particle size and in vivo exposures, where the nanosuspensions provided the highest exposure. Furthermore, no adverse events were observed for the substance nor the nanosuspension formulations (i.e., the particles) in spite of the higher exposures obtained with the nanoparticles. To make it possible to calculate the bioavailability, 5 μmol/kg doses of the nanosuspensions (5 ml/kg) were also administered intravenously. No adverse events were observed. Conclusions: The nanoparticles have a larger surface, resulting in faster in vivo dissolution rate, faster absorption, and increased bioavailability, compared to microparticles. The lower overall bioavailability observed at the high dose, compared with the low dose, was due to a combination of low dissolution rate, low solubility, and a narrow intestinal absorption window for UG558.     

Characterization and Evaluation of Tenoxicam Coprecipitates

Tenoxicam is a nonsteroidal anti-inflammatory drug belonging to the oxicam group. The drug is slightly soluble in water. In a trial to increase its dissolution, different commonly used excipients were selected to prepare coprecipitates with tenoxicam. The coprecipitates were prepared using the solvent evaporation method, and the ratio used was 1:3 drug to additive. The prepared coprecipitates were subjected to a dissolution study, and they were characterized using infrared (IR) and differential scanning calorimetry (DSC) techniques. Dissolution profiles of most of the prepared coprecipitates demonstrated higher dissolution than pure tenoxicam. The characteristic peaks of tenoxicam in the IR spectrum disappeared in the spectra of all the prepared coprecipitates except those prepared with sodium chloride, for which the IR spectrum was identical to that of the pure drug. The characteristic peaks of tenoxicam disappeared in the DSC thermograms of the coprecipitates under study, indicating a change in structure from pure tenoxicam. Characterization of the coprecipitates by IR and DSC techniques revealed structural changes in the prepared coprecipitates from the plain drug, which may account for increased dissolution rates.     

THE DISSOLUTION OR GROWTH OF A SPHERE

The problem of the dissolution or growth of an isolated, stationary, sphere in a large fluid body is analyzed. The motion of the boundary as well as the resulting motion in the liquid are properly taken into account. The governing equations are solved using a recently developed technique (Subramanian and Weinberg, 1981) which employs an asymptotic expansion in time. Results for the radius of the sphere as a function of time are calculated. The range of utility of the present solution is established by comparison with a numerical solution of the governing equations obtained by the method of finite differences.     

The Effect of Silver Chloride Formation on the Kinetics of Silver Dissolution in Chloride Solution

The precipitation and growth of AgCl on silver in physiological NaCl solution were investigated. AgCl was found to form at bottom of scratches on the surface which may be the less effective sites for diffusion or the favorable sites for heterogeneous nucleation. Patches of silver chloride expanded laterally on the substrate until a continuous film formed. The ionic transport path through this newly formed continuous film was via spaces between AgCl patches. As the film grew, the spaces between AgCl patches closed and ion transport was primarily via micro-channels running through AgCl patches. The decrease of AgCl layer conductivity during film growth were attributed to the clogging of micro-channels or decrease in charge carrier concentration inside the micro-channels. Under thin AgCl layer, i.e. on the order of a micrometer, the dissolution of silver substrate was under mixed activation-Ohmic control. Under thick AgCl layer, i.e. on the order of tens of micrometers, the dissolution of silver substrate was mediated by the Ohmic resistance of AgCl layer.     

Anodic behavior of gold in 1-butyl-3-methylimidazolium methanesulfonate ionic liquid with chloride anion

The anodic behavior of gold has been investigated in presence of chloride and/or water in 1-butyl-3-methylimidazolium methanesulfonate (BMI CH₃SO₃) ionic liquid (IL). The cyclic voltammetry (CVs) in presence of chloride ions shows two waves attributed to the oxidation of the gold electrode which occurs under two steps: the first one is attributed to the electrochemical dissolution of gold into to gold(I), while the second one is attributed to an overlap of the chloride oxidation step as well as the oxidation of Au(I) to Au(III). Furthermore the determination of water and chloride content in IL allowed observing that the passive layer induced by water could be removed under chloride. Thanks to those results we were able to clarify the conditions of gold recovering in this kind of electrolyte.     

Structural effects on trends in the deposition and dissolution of metal-supported metal adstructures

A simple thermodynamic formalism is combined with Density Functional Theory calculations to determine periodic trends in the reversible deposition/dissolution potentials of admetals on a variety of transition metal substrates. For each admetal/substrate combination (81 in total), the deposition/dissolution potential shift (referenced to the corresponding potential of the admetal in its bulk, elemental form) is calculated for isolated adatoms, for dimers, and for more extended kink structures. Clear periodic trends are found for the potential shifts across the space of different admetals and substrates. In addition, for the significant majority of these admetal/substrate systems, the structural effects are found to be a strong function of the local coordination number of the metal atoms, thereby verifying an important assumption that has been widely used in semiempirical models of deposition and dissolution.     

Study of Formulation Parameters by Factorial Design in Metoprolol Tartrate Matrix Systems

The study of formulation parameters in hydrophilic matrices of metoprolol tartrate by 2³ factorial design was made. We compared the dissolution profiles of two hydrophilic polymers (hydroxypropylmethylcellulose and hydroxyethylcellulose) at high and low concentrations and in the presence or absence of an insoluble excipient (calcium hydrogen phosphate dihydrate). The results showed that the presence of an insoluble excipient influenced almost all of the dissolution parameters.     

Effect of Grain Boundary on the Wettability and Interfacial Morphology in the Molten Bi／Cu System

The wetting behavior of molten Bi on polycrystalline Cu substrate and single crystal Cu substrate was studied by the sessile drop method in the temperature range from 673 to 873K. At low temperature the wetting behaviors of molten Bi on both types of Cu substrate were similar. However, at high temperature, the equilibrium contact angle of polycrystalline Cu substrate was lower than that of single crystal Cu substrate, because the preferred dissolution of grain boundaries leads to a smaller liquid/solid interracial energy for polycrystalline Cu substrate. The formation mechanism of arrow-shaped Cu grains at the Bi/single crystal Cu interface is also discussed.