Number Of Particles In Solution Research Articles

Many-Particle Limits in Molecular Solvation

In this paper, the authors study the limit of a sharp interface model for the solvation of charged particles in an implicit solvent as the number of solute particles and the size of the surrounding box tend to infinity. The energy is given by a combination of local terms accounting for the physical presence of the particles in the solvent and a nonlocal electric energy with or without an ionic effect. In the presence of an ionic effect, the authors prove a screening effect in the limit, i.e., the limit is completely localized and hence electric long-range interactions of the particles can be neglected. In the absence of the ionic effect, the authors show that the behavior of the energy depends on the scaling of the number of particles with respect to the size of the surrounding box. All scaling regimes are identified and corresponding limit results proved. In regimes with many solute particles this limit includes electric interactions of $$H^{-1}$$-type between the particles.

Analyzing Subvisible Particles in Protein Drug Products: a Comparison of Dynamic Light Scattering (DLS) and Resonant Mass Measurement (RMM)

Aggregation is common in protein drug manufacture, and while the effects of protein particulates are under investigation, many techniques applicable for their characterization have been recently developed. Among the methods available to characterize and quantify protein aggregates, none is applicable over the full size range and different methods often give conflicting results. The studies presented here compare two such methods: dynamic light scattering (DLS) and resonant mass measurement (RMM). The performance of each method was first characterized using polystyrene particle size standards (20, 60, 100, 200, 400, and 1,000 nm) over a range of concentrations. Standard particles were measured both singly and in binary mixtures containing 20 nm particles at a fixed concentration (10(14) particles/mL) and various concentrations of one of the other particle sizes (i.e., 60, 100, 200, 400, or 1,000 nm). DLS and RMM were then used to detect unknown aggregate content in stressed samples of IgG. Both instruments were shown to have a working range that depends on particle size and concentration. In binary mixtures and polydisperse solutions, DLS was able to resolve two species in a manner dependent on both concentration and particle size. RMM was able to resolve particles above 200 nm (150 nm for protein) at concentrations below 10(9) particles/mL. In addition, dilution was evaluated as a technique to confirm and quantify the number of particles in solution.

Reducing harm from injecting pharmaceutical tablet or capsule material by injecting drug users

It has long been known that drug users may use a variety of pharmaceutical preparations by injection, many of which are not intended for intravenous administration (e.g. buprenorphine, methylphenidate, oxycodone). The introduction of tablet fillers such as talc or starch, in the blood circulation may cause, besides local injection site complications, pulmonary emboli. To reduce the harmful consequences of injecting such solutions, drug users have been encouraged to use filters. This research studied the effectiveness of an injection drug user syringe filter (IDUSF) in eliminating these particles. Generic buprenorphine and methylphenidate (Ritaline®), both containing talc, are frequently diverted for use by injection in France. The aim of our laboratory-based study was to compare the effectiveness of an IDUSF (Sterifilt®, filter pore size = 10 µm) versus no filtration, at reducing the number of particles in solutions of dissolved generic buprenorphine and Ritaline®. Compared with a non-filtered solution drawn up through a 30G needle, filtering of the generic buprenorphine solution eliminated approximately 85% of all particles between 1 and 5 µm in diameter and 97% of particles between 5 and 18 µm. In the Ritaline® solution, these values were two-thirds and 95%, respectively. Preliminary results indicate that IDUSF are effective in significantly filtering out large particles, which are responsible for major harms like pulmonary emboli. One strategy for alleviating these consequences is to promote the implementation of IDUSF in harm reduction programs, accompanied by training of social workers, peers and drug users.

The Irrationality of the Present Use of the Osmole Gap

The present clinical use of serum osmometry is erroneous in two respects. The first, and the most important, is the incorrect assumption that serum behaves as a dilute 'ideal' solution and that the osmotic activity of a substance depends solely on the number of solute particles. The amount of variance from ideal behaviour of serum containing an exogenous substance is expressed by the osmotic coefficient (phi). We have calculated the osmotic coefficient for serum containing ethanol (alcohol) and recommend that the osmotic coefficient for serum containing other low molecular weight substances such as methanol (methyl alcohol), isopropyl alcohol and ethylene glycol also be calculated. This is necessary for the accurate calculation of the contribution of these substances to the serum osmolality.Secondly, the practice of subtracting the calculated serum molarity from measured serum osmolality is not valid since it represents a mathematically improper expression. The units of these two terms are different. The 'osmole gap' (OG) is typically viewed as the difference between serum osmolality determined by an osmometer and the estimated total molarity of solute in serum by directly measuring the concentration of several substances and then substituting them into a published formula. Some authors call this sum the calculated or estimated osmolarity but, because the concentrations are measured directly and not with an osmometer, the calculated term represents molarity. The units of osmolality are mmol/kg of H2O and the units of molarity are mmol/L. Therefore, the practice of subtracting calculated serum molarity from measured serum osmolality is not mathematically sound and is an oversimplification for ease of application. This mathematical transgression necessarily adds an error to the incorrectly calculated OG. Despite this, the OG is commonly used in clinical medicine. Serum osmolality can be converted to molarity provided the weight percentage and the density of the solution are known and thus, we recommend that this conversion be done prior to calculation of the gap. We recommend that the gap between measured serum osmolarity and calculated serum molarity be called the 'osmolar gap'. After having corrected for non-ideality for serum and for inconsistency of units, the standard value and reference range for this gap must be determined in an adequate number of patient populations and in a variety of clinical settings. An example of this determination, using data from a group of ethanol-poisoned patients is given. This correction should be applied before the evaluation of the osmolar gap as a screening test for other low molecular weight substances proceeds.

Measurement of urine relative density using refractometer and reagent strips.

The relative density of urine is the ratio of its density to that of water and depends on both the number and weight of solute particles in the sample, while osmolality depends only on the number of solute particles. Water metabolism is regulated by the interaction of the renal medullary countercurrent system with the circulating levels of antidiuretic hormone and thirst. The concentration of solids in urine can be measured by weighing, hydrometry, oscillations of a capillary tube, refractometry and reagent strip. These techniques, interrelated but not identical, are commonly used in hospital laboratories and in clinical wards. We compared the results obtained in 1725 urine samples of inpatients and outpatients using an automated refractometer to those obtained using two visually read dip stick tests. The correlation coefficients (Super Aution analyser vs. Aution Sticks 10EA, Aution Sticks 10 EA vs. N-Multistix, Super Aution analyser vs. N-Multisticks were 0.663, 0.645 and 0.514, respectively) and the great dispersion of mountain plots demonstrates that different techniques are not interchangeable in the measurement of relative density. Since the results obtained after discarding the samples with pH higher than 7 and those containing glucose or protein were very similar to the ones reported above, the role of these interferents appears negligible in inducing the discrepancy.

A new method for measuring human basic tear fluid osmolality.

Osmolality measures the total number of particles dissolved in a kilogram of water. Since the colligative properties of a solution depend primarily on the number of particles in solution, a measurement of any of these properties can, in principle, be used as the basis for determining osmolality. Freezing (melting) point determinations are a sensitive and well-established method for determining osmolality.

Self-Association of Nicotinamide in Aqueous Solution: Light-Scattering and Vapor Pressure Osmometry Studies

Nicotinamide is a hydrotropic agent that has been reported to self-associate in aqueous solution. The objective of this study is to characterize the self-association of nicotinamide with regard to the extent of self-association as well as association constants using light-scattering and vapor pressure osmometry. Both methods allow calculation of association constants; however, while light-scattering measurements depend on the size of particles in solution, vapor pressure osmometry depends on the number of particles in solution. Using light-scattering, nicotinamide was found to associate primarily as dimers and trimers. Higher order aggregates can be characterized by an average aggregation number of 4.37. The association constants were 9.99 L/mol and 13.1 L/mol for dimerization and trimerization, respectively. From vapor pressure osmometry data were calculated a dimerization constant of 0.203 L/mol and a trimerization constant of 14.1 L/mol. In comparison, the trimerization constants are in good agreement, while the dimerization constants differ by an order of magnitude. Since light-scattering measurements are less reliable for small molecules like nicotinamide at low concentrations, it is felt that the dimerization constant calculated from vapor pressure osmometry is the more accurate.

Relative density of urine: methods and clinical significance.

The physical properties and chemical composition of urine are highly variable and are determined in large measure by the quantity and the type of food consumed. The specific gravity is the ratio of the density to that of water, and it is dependent on the number and weight of solute particles and on the temperature of the sample. The weight of solute particles is constituted mainly of urea (73%), chloride (5.4%), sodium (5.1%), potassium (2.4%), phosphate (2.0%), uric acid (1.7%), and sulfate (1.3%). Nevertheless, urine osmolality depends only on the number of solute particles. The renal production of maximally concentrated urine and formation of dilute urine may be reduced to two basic elements: (1) generation and maintenance of a renal medullary solute concentration hypertonic to plasma and (2) a mechanism for osmotic equilibration between the inner medulla and the collecting duct fluid. The interaction of the renal medullary countercurrent system, circulating levels of antidiuretic hormone, and thirst regulates water metabolism. Renin, aldosterone, prostaglandins, and kinins also play a role. Clinical estimation of the concentrating and diluting capacity can be performed by relatively simple provocative tests. However, urinary specific gravity after taking no fluids for 12 h overnight should be 1.025 or more, so that the second urine in the morning is a useful sample for screening purposes. Many preservation procedures affect specific gravity measurements. The concentration of solids (or water) in urine can be measured by weighing, hydrometer, refractometry, surface tension, osmolality, a reagent strip, or oscillations of a capillary tube. These measurements are interrelated, not identical. Urinary density measurement is useful to assess the disorders of water balance and to discriminate between prerenal azotemia and acute tubular necrosis. The water balance regulates the serum sodium concentration, therefore disorders are revealed by hypo- and hypernatremia. The disturbances are due to renal and nonrenal diseases, mainly liver, cardiovascular, intestinal, endocrine, and iatrogenic. Fluid management is an important topic of intensive care medicine. Moreover, the usefulness of specific gravity measurement of urine lies in interpreting other findings of urinalysis, both chemical and microscopical.

The wave vector dependence of diffusion coefficients in photon correlation spectroscopy of protein solutions

The mutual diffusion coefficient Dm was measured by means of photon correlation spectroscopy (PCS) for bovine serum albumin (BSA) at pH 4.7 and ionic strength I≃0.12 M. The BSA concentrations ranged from 1.00 to 10.7 g/dℓ and the magnitude of the scattering wave vector K varied from 3.21×104 to 3.51×105 cm−1. It was found that Dm=D0[1−(0.0166±0.0009)C], where D0=(5.92±0.04)×10−7 cm2/s corrected to water at 20 °C and the C measured in units of g/dℓ. The quantity Cn/K3, where Cn is the concentration in number of solute particles per cm3, ranged from 2 to 27 000, but this had no influence on the measured values of Dm. This work does not support the idea that the small size of K−1 or the small number of molecules contained in the volume K−3 affects the magnitudes of diffusion coefficients determined by PCS for proteins at moderate ionic strengths.

Determinations of Sodium Chloride Equivalents by Osmometry

AbstractThe vapor pressure osmometer was used to calculate the sodium chloride equivalents of several compounds. These values were compared with published values and in some cases, considerable variation was seen. The osmolality was determined for iso-osmotic drug solutions mixed in different ratios with iso-osmotic saline or sorbitol. The drugs investigated included atropine sulfate, te-tracycline hydrochloride, homatropine hydrobromide, pilocarpine nitrate, amphetamine sulfate and bromodiphenhydramine hydrochloride. The results of these studies showed that colligative properties of multicomponent aqueous solutions are often non-additive in manner. The changing osmolality suggests that ion-ion or ion-molecule forces are occurring and when osmolality increases, so does the number of particles in solution.

An osmometer model for changes in the buoyant density of chromaffin granules

We present a model for the structure of isolated bovine adrenal medulla chromaffin granules derived from the dependence of granule density on the osmotic pressure of the suspension medium at 2 degrees C. The granule consists of a flexible, inelastic membrane bounding an osmotically active core. The core consists of a solution space and a separate, nonosmotic phase. Since the granule behaves like a "perfect" osmometer over a wide range of osmolarities, we conclude that (a) within these limits, the core consists of a constant amount of condensed material and a constant number of particles in solution, (b) from the constraints of the osmometer model, the osmolality inside the granule must equal the osmolality outside. Therefore the high concentrations of catecholamines (greater than 0.7 M) and ATP (greater than 0.18 M) measured biochemically cannot be dissolved in the core solution as separate molecules, but must be condensed into larger aggregates. These results are supported by electron micrographic examination of the effect of osmotic pressure changes on granule morphology.

Effects of agitation on size distribution of particulate matter in large-volume parenterals.

The particle-size distributions of six types of large-volume parenterals subjected to different degrees of agitation were determined using an automatic particle counter. Data acquired from each solution, which had been maintained in a stored condition, subjected to agitation by inverting 20 times, and then mechanically shaken for 30 min, produced a linear relationship between log N greater than D and log D. Both the slope (K) and the number of particles per milliliter exceeding 1 micrometer in diameter (N greater than 1) exhibited a dependence on the degree of agitation. Their combined effect indicates that agitation by 20 hand inversions removed particulate matter from the surface of the container, which increased the total number of particles in solution (greater than 1 micrometer) but did not significantly alter the relative size distribution. Agitation for 30 min, however, disintegrated agglomerates and produced a particle-size distribution with a greatly increased number of particles whose diameters were less than 1 micrometer and a corresponding decrease in the number of particles exceeding 1 micrometer in diameter. The particle-size distribution of a parenteral solution determined by this in situ instrumental method was, therefore, dependent upon the degree of agitation to which the parenteral was subjected prior to examination.

Osmolality and Other Chemical Determinations in Postmortem Human Vitreous Humor

The measurement of osmotic pressure in blood and urine has been used extensively in clinical investigation and is beginning to be available as a diagnostic test in the hospital laboratory [1–4]. It is dependent on the number of solute particles in solution, rather than their shape, weight, or charge. The determination of the freezing point depression of a solution gives a good estimate of the number of particles and is the basis for the calculation of the osmolality. Serum osmolality has a normal range of 275 to 295 mOsm/kg, with electrolytes, particularly sodium, contributing over 90 percent of this value. Glucose, nonprotein nitrogen, and protein substances make up a large portion of the remainder. The average osmolality of urine ranges from 300 to 1090 mOsm/kg, varies with dietary intake, and is generally higher in males [3]. The mean value for cerebrospinal fluid osmolality in fifty living patients was found to be 281 mOsm/kg, and the range of values extended from 269 to 304 mOsm/kg [5]. Postmortem spinal fluid studies to date have not included osmolality determinations.

Short-Range Interactions of Aqueous Ions

Data on the 1–1 fluoride complex ion with noble-gas-type cations are examined for information on short-range ion—ion and water—ion interactions. A four-term numerical correlation of the standard free energies with the size and charge of the ion is developed based on the approach that electric saturation is not directly important to the complex formation. Deviations from the classical point charge Coulomb energy are expressed by a term independent of temperature and the dielectric medium, exponential in the separation distance, and containing only fundamental quantities which suggest wave-mechanical interaction between cation and anion. The total standard entropy change separates into three terms; the temperature dependence of the macroscopic dielectric constant, the removal of coordinated water, and the cratic term for the change in the number of solute particles. A screened charge model of the hydrated ion is proposed in which hydration is the loss of the quantum-mechanical free energy of the gaseous ions by the formation of covalent bonds with the water. The ion charge is delocalized, spreading out to the coordinated water. The degree of hydration depends on the free energy of the water, with the free energy for coordination of the last water molecule being less than 1 kcal.