An aqueous concentration model for riverine spills.

A numerical model is developed to predict the aqueous concentrations of sparingly soluble compounds resulting from oil, fuel, or chemical spills onto rivers. The model computes the concentration of compounds both in the slick phase and in the aqueous phase by simulating the processes that affect the fate of the spilled compound. Processes simulated by the model include spreading and drifting of the surface slick, evaporation from the slick, dissolution from the slick into the water, volatilization from the water, and longitudinal dispersion in the river. The model is used to simulate a hypothetical spill of jet fuel, demonstrating that the concentration of a compound in the aqueous phase is strongly linked to its concentration in the slick phase. The most soluble and most volatile compounds exhibit the highest aqueous concentrations in the early stages of the spill, but ultimately the less soluble and less volatile compounds reach the highest aqueous concentrations. Streamwise concentration gradients in the slick due to the rapid evaporation of the more volatile compounds are shown to have an effect on the aqueous concentration.     

Comparison of Solid-Liquid and Liquid-Liquid Mass Transfer

Mass transfer from solutions of m-acetotoluide, phenacetin and salicylamide into a stationary solvent, water, was studied. A sharp concentration jump was found at the leading solute front for all three liquid-liquid systmes. A comparison was made between the mass transferred in solid-liquid and liquid-liquid systems. The dissolution of m-acetotoluide, phenacetin and salicylamide was compared with mass transfer of solute from solutions with concentrations C_i, 2C_i and C_s into the pure solvent. In all cases, the amount dissolved from the solid was approximated by the C_i or the 2C_i-solvent system with the amount transferred in the C_s-solvent system approximately 100 fold greater than was dissolved from the solid. It was concluded that a concentration much less than saturation exists at the solid-liquid interface and that dissolution of the three compounds studied is controlled by the rate of solvent interaction at the solid surface.     

Surface state improvement of ground AT and SC quartz cuts by controlled dissolution in NaOH,KOH, LiOH

After the studies which allowed us to perfect the chemical thinning down, or controlled dissolution, of both AT and SC quartz plates in NaOH and KOH media, respectively, we have investigated mixtures of these with another basic compound (LiOH) in order to discover a common solvent for both AT and SC cuts. The results show that crystallographic orientation and solvent nature have a great influence on controlled dissolution especially on the surface texture. It appears that the basic compound which has the smallest cation imposes its properties and consequently, the chemical polishing of both AT and SC cuts cannot be made in good conditions with the same solvent.     

Production of powders and films by the rapid expansion of supercritical solutions

A new process utilizing the rapid expansion of supercritical fluid solutions (RESS) is described for the production of fine powders and thin films by the rapid nonequilibrium precipitation of nonvolatile compounds from dense gas solutions upon expansion. A variety of the fluid solution expansion parameters, including solute and solvent identity, solute concentration, expansion temperature, and expansion nozzle configuration, has been shown to affect the product characteristics of materials formed during the RESS process. Conditions favouring thin film formation include very dilute solutions and short nozzles minimizing residence time during expansion. Particle formation is favoured by more concentrated solutions. The process has been demonstrated to produce products of widely varying morphology by the adjustment of RESS parameters, and examples of SiO₂ GeO₂ and various polymeric materials are presented. Unique features of the RESS process relevant to other powder and film production methods are described and potential applications are discussed.     

Comparison of Solid-Liquid and Liquid-Liquid Mass Transfer

Abstract

Mass transfer from solutions of m-acetotoluide, phenacetin and salicylamide into a stationary solvent, water, was studied. A sharp concentration jump was found at the leading solute front for all three liquid-liquid systmes. A comparison was made between the mass transferred in solid-liquid and liquid-liquid systems. The dissolution of m-acetotoluide, phenacetin and salicylamide was compared with mass transfer of solute from solutions with concentrations C_i, 2C_i and C_s into the pure solvent. In all cases, the amount dissolved from the solid was approximated by the C_i or the 2C_i-solvent system with the amount transferred in the C_s-solvent system approximately 100 fold greater than was dissolved from the solid. It was concluded that a concentration much less than saturation exists at the solid-liquid interface and that dissolution of the three compounds studied is controlled by the rate of solvent interaction at the solid surface.     

Selection of oral bioavailability enhancing formulations during drug discovery

The objective of this paper was to identify oral bioavailability enhancing approaches for a poorly water-soluble research compound during drug discovery stages using minimal amounts of material. LCQ789 is a pBCS (preclinical BCS) Class II compound with extremely low aqueous solubility (<1 μg/mL) and high permeability, therefore, resulting in very low oral bioavailability in preclinical species (rats and dogs). A number of solubility and/or dissolution enhancing approaches including particle size reduction, solid dispersions, lipid-based formulations and co-crystals, were considered in order to improve the compound's oral bioavailability. High-Throughput Screening (HTS) and in silico modeling (GastroPlus?) were utilized to minimize the compound consumption in early discovery stages. In vivo evaluation of selected physical form and formulation strategies was performed in rats and dogs. Amongst the formulation strategies, optimized solid dispersion and lipid-based formulation provided significant improvement in drug dissolution rate and hence, oral bioavailability. In addition, a significant impact of physical form on oral bioavailability of LCQ789 was observed. In conclusion, a thorough understanding of not only the formulation technique but also the physical form of research compounds is critical to ensure physical stability, successful pharmacokinetic (PK) profiling and early developability risk assessment.     

Preparation and characterization of coenzyme Q10-Eudragit solid dispersion

A solid dispersion of Coenzyme Q10 and Eudragit L 100-55 was prepared using solvent evaporation method. Solid dispersion, physical mixture, and pure compound were then characterized using differential scanning calorimetry and powder x-ray diffraction. Solubility of CoQ10 in different surfactant media was measured, and a suitable dissolution medium was developed to compare the dissolution patterns of the solid dispersion, physical mixture, and the pure compound. Combining labrasol with different surfactants in dissolution media demonstrated an additive effect on CoQ10 solubility. The solubility of CoQ10 in a 4% Labrasol/2% Cremophor EL solution was 562 microg/ml, which was five times higher than the combined solubility in 5% Labrasol (91 microg/ml) and 5% Cremophor EL (7.8 microg/ml). Moderate change in the crystalline pattern of CoQ10 was observed, which was attributed to solvent displacement rather than the degree of crystallinity change. The dissolution test indicated that the in-vitro release of Coenzyme Q10 from its solid dispersion was much faster than its physical mixture, which in turn was faster than the pure drug. The amount of drug released in 12 hours from solid dispersion, physical mixture, and the pure drug was 100, 26.5 and 12.5% respectively. CoQ10 was photostable throughout the dissolution experiments.     

The use of acoustic emission techniques to monitor fracture processes in high strength precipitation hardened aluminum alloys

The ductile fracture of dispersion hardened aluminum alloy containing brittle intermetallic inclusions is briefly reviewed. The effect of the size, distribution and chemical composition of the inclusions in affecting the matrix fracture behavior is discussed.The potential of acoustic emission techniques in being able to discriminate between different microstructures produced by various thermomechanical treatment is emphasized. It is shown that processes that affect dislocation motion, i.e., cold work, precipitation, solute atom diffusion, etc., also affect the acoustic response, thus making the AE technique extremely useful for the study of flow and fracture behavior of aluminum alloys.     

Power-law decay in rate of solute removal from ground water with various exponents associated with matrix diffusion in granular packed bed

Power-law decay of pollutant concentration in flushing gas is often observed during the remediation of contaminated groundwater. However, the underlying mechanisms that cause the power law are not clear in many cases and the variations of the exponent of the power law can not be explained by the existing models with a solid physical basis. In order to obtain a variety of the values of exponent, we propose a simple two-fluid cubic lattice model. We first created a complex interfacial geometry between gas and liquid in a granular packed bed using a percolation model, and then calculated the removal rate of solute with matrix diffusion by performing the random walk of solute particles in the invaded liquid phase until the random walkers of solute reach to the gas/liquid interface. A significant power law was observed in the dissipation rate of solute particles with the proposed model. As the saturation of the invading gas in the matrix increases, the absolute value of exponent increased from 0.5, up to approximately 1.0, which cannot be reproduced by the previous analytical models. We successfully showed that the matrix diffusion with a complicated gas/liquid interface causes the power-law behavior with various exponents.     

Rapid nondestructive spectrometric measurement of temperature-dependent gas-liquid solubility equilibria

Gas-liquid solubility equilibria (Henry's Law behavior) are of basic interest to many different areas. Temperature-dependent aqueous solubilities of various organic compounds are of fundamental importance in many branches of environmental science. In a number of situations, the gas/dissolved solute of interest has characteristic spectroscopic absorption that is distinct from that of the solvent. For such cases, we report facile nondestructive rapid measurement of the temperature-dependent Henry's law constant (K(H)) in a static sealed spectrometric cell. Combined with a special cell design, multiwavelength measurement permits a large range of K(H) to be spanned. It is possible to derive the K(H) values from the absorbance measured in the gas phase only, the liquid phase only (preferred), and both phases. Underlying principles are developed, and all three approaches are illustrated for a solute like acetone in water. A thermostatic spectrophotometer cell compartment, widely used and available, facilitates rapid temperature changes and allows rapid temperature-dependent equilibrium measurements. Applicability is shown for both acetone and methyl isobutyl ketone. Very little sample is required for the measurement; the K(H) for 4-hydroxynonenal, a marker for oxidative stress, is measured to be 56.9 ± 2.6 M/atm (n = 3) at 37.4 °C with 1 mg of the material available.     

III. Segregation of Active Constituents from Tablet Formulations During Grinding: Effects on Coated Tablet Formulations

Grinding or milling coated tablets in preparation for their assay can cause the physical separation of an active ingredient from the coating and other tablet components. This phenomenon has been shown to partially account for the poor reproducibility between duplicate assays, and for discrepancies among assays for the same group of tablets but which were composited by different methods.

The effect of compositing methods on the assay results is shown with commercial enteric coated aspirin tablets from various manufacturers. Samples for assay were prepared by manual grinding with a glass mortar and pestle, mechanical grinding with an electric tablet grinder, direct dissolution of the tablets in a suitable solvent, and uncoating of the tablets with an organic solvent prior to their manual grinding.

Suggestions are offered to minimize the effects of segregation of an active tablet ingredient during grinding or milling on the assay results.     

Purification process by solution zone passages

The travelling heater zone-refining process and its relation to the travelling solvent and travelling heater methods of growing single crystals are described. The variation of the zone composition during the zone passage is derived, proceeding from the solute-impurity-solvent diagrams, and the impurity distribution along the crystallisate, after a zone passage, is derived, by considering that the solute and the impurity form either a solid solution or an eutectic. The influence of the parameters which determine the distribution is discussed. The impurity distribution along the crystallisate after a number of zone passages is derived. The application of the process is suitable in the case of a sub-unity distribution coefficient, the zone passage efficiency being higher, the smaller the distribution coefficient and the steeper the slope of the dissolution straight line. The process is particularly advantageous when the solute and the impurity form an eutectic. It is advantageous to select a high dissolution temperature, close to the solvent boiling temperature, and a crystallisation temperature as near as possible to the dissolution temperature, when the solute and the impurity form either a solid solution or an eutectic.     

Solubility and dissolution enhancement strategies: current understanding and recent trends

Identification of lead compounds with higher molecular weight and lower aqueous solubility has become increasingly prevalent with the advent of high throughput screening. Poor aqueous solubility of these lipophilic compounds can drastically affect the dissolution rate and subsequently the drug absorbed in the systemic circulation, imposing a significant burden of time and money during drug development process. Various pre-formulation and formulation strategies have been applied in the past that can improve the aqueous solubility of lipophilic compounds by manipulating either the crystal lattice properties or the activity coefficient of a solute in solution or both, if possible. However, despite various strategies available in the armor of formulation scientist, solubility issue still remains an overriding problem in the drug development process. It is perhaps due to the insufficient conceptual understanding of solubility and dissolution phenomenon that hinders the judgment in selecting suitable strategy for improving aqueous solubility and/or dissolution rate. This article, therefore, focuses on (i) revisiting the theoretical and mathematical concepts associated with solubility and dissolution, (ii) their application in making rationale decision for selecting suitable pre-formulation and formulation strategies and (iii) the relevant research performed in this field in past decade.     

Time-evolving collagen-like structural fibers in soft tissues: biaxial loading and spherical inflation

This work considers a previously developed constitutive theory for the time dependent mechanical response of fibrous soft tissue resulting from the time dependent remodeling of a collagen fiber network that is embedded in a ground substance matrix. The matrix is taken to be an incompressible nonlinear elastic solid. The remodeling process consists of the continual dissolution of existing fibers and the creation of new fibers. Motivated by experimental reports on the enzyme degradation of collagen fibers, the remodeling is governed by first order chemical kinetics such that the dissolution rate is dependent upon the fiber stretch. The resulting time dependent mechanical response is sensitive to the natural configuration of the fibers when they are created, and different assumptions on the nature of the fiber’s stress free state are considered here. The response under biaxial loading, a type of loading that has particular significance for the characterization of biological materials, is studied. The inflation of a spherical membrane is then analyzed in terms of the equal biaxial stretch that occurs in the membrane approximation. Different assumptions on the natural configuration of the fibers, combined with their time dependent dissolution and reforming, are shown to emulate alternative forms of creep and relaxation response. This formal similarity to viscoelastic phenomena occurs even though the underlying mechanisms are fundamentally different from the mechanism of macromolecular reconfiguration that one typically associates with viscoelastic response.     

II. Segregation of Active Constituents from Tablet Formulations During Grinding: Significance to Pharmaceutical Analysis

The preparatory step in the analysis of active drugs in tablet dosage forms has generally consisted of the grinding or milling of a given number of the tablets into a fine powder. Certain drugs formulated as tablets have been shown to undergo physical separation from other tablet components as a result of grinding. This phenomenon accounts, at least in part, for the poor reproducibility found in duplicate assays for these drugs in tablet composites. This same phenomenon also explains discrepancies between the average of the individual tablet assay values of samples prepared by direct dissolution, and the assay value of the corresponding composites.

This paper illustrates this phenomenon using a problem dosage form and suggests methods of sample preparation that avoid segregation of ingredients. These methods include the direct dissolution of a representative number of individual tablets in a suitable solvent, the sieving and regrinding of the ground tablets, the grinding of a composite with a suitable organic solvent and the evaporation of the solvent, and the dissolution of the total composite tablet sample in a solvent.     

Nonfoaming adsorptive bubble separation processes

Two nonfoaming separations, bubble fractionation and solvent sublation, are reviewed. These unit operations are interfacial (gas bubble-liquid) separation techniques that have significant potential for the removal of several metal ions and hydrophobic organic compounds of environmental significance from aqueous solutions. Experimental and theoretical work on the two processes relating the effects of process variables are summarized. The underlying mechanisms of the two processes are identical although solvent sublation is found to have significant advantages over bubble fractionation, air stripping, and the related process of solvent extraction. Specifically, sublation can achieve a greater degree of removal than extraction, can remove both volatile and nonvolatile compounds, unlike air stripping, and has less sensitivity to axial dispersion than bubble fractionation. The potential use of these processes for large-scale separations is examined; the limitations and need for further work are clearly evident. Questions of scale-up, bubble generation, and reduction of axial dispersion all require further investigation.     

III. Segregation of Active Constituents from Tablet Formulations During Grinding: Effects on Coated Tablet Formulations

Abstract

Grinding or milling coated tablets in preparation for their assay can cause the physical separation of an active ingredient from the coating and other tablet components. This phenomenon has been shown to partially account for the poor reproducibility between duplicate assays, and for discrepancies among assays for the same group of tablets but which were composited by different methods.

The effect of compositing methods on the assay results is shown with commercial enteric coated aspirin tablets from various manufacturers. Samples for assay were prepared by manual grinding with a glass mortar and pestle, mechanical grinding with an electric tablet grinder, direct dissolution of the tablets in a suitable solvent, and uncoating of the tablets with an organic solvent prior to their manual grinding.

Suggestions are offered to minimize the effects of segregation of an active tablet ingredient during grinding or milling on the assay results.     

Experiments on interaction of liquid tin with solid copper

Abstract

The reaction of liquid tin with solid copper has been studied by heating small volumes ofpure tin on copper coupons at various temperatures and times, and evaluating the resulting reaction metallographically. Three reaction temperatures were used:260,400,and450 ° C. Specimen geometry was chosento simulate a typical solder joint. The reaction was observed to occur in two stages: an initial fast stage with copper/liquid tin interface movement rates from 0.2 μm s^-1 at260 ° C to 0.8 μm s^-1 at 450 ° C, followed by a much slower stage. It was concluded that the first stage corresponds to direct dissolution of copper in liquid tin up to or beyond the liquidus concentration for the reaction temperature used.This is followed by the formation of an intermetallic compound layer atthe copper/liquid interface. Subsequent copper dissolution then occurs by solid state diffusion through the compound layer, a much slower process than direct dissolution.     

Dynamic X-radiography of liquid sodium

The dissolution process of gold and silver wires in liquid sodium was observed as an example of a system in which there is a high density difference between solvent and solute. The solidification sequence of the alloys formed by the dissolution process was also observed. Sodium is very difficult to analyse metallographically, using optical microscopy or electron beam techniques, due to the high reactivity of sodium with the water vapour present in the air. In this work, a method was evolved for observing the behaviour of liquid sodium, when used as a solvent in dissolution experiments, utilizing X-radiography. Sample cans were irradiated with a beam of X-rays and the transmitted beam fell on a fluorescent screen image intensifier. This was either viewed directly using a closed-circuit TV system or recorded using video recording equipment. In the future it is hoped to extend this work to other light-heavy metal systems such as the Al-Cu alloys.On attachment from Sheffield University, Western Bank, Sheffield, UK.