SEARCH · PubMed Health

Results for “Solubility”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 955 records · Page 53Linked to original sources

PubMed1985

Strategies in the design of solution-stable, water-soluble prodrugs II: properties of micellar prodrugs of methylprednisolone.

In a previous study, a physical-organic approach to the design of solution-stable, water-soluble prodrugs of the corticosteroid methylprednisolone was outlined, and several 21-esters were synthesized to test the approach. Compounds exhibiting dilute solution stabilities approaching 2 years at 25 degrees C were reported. A complicating factor in more concentrated aqueous solutions of water-soluble prodrugs, however, is the limited extent to which hydrolysis can occur before the solution becomes saturated with respect to the relatively insoluble parent drug. In this study the advantages of micellar prodrugs as water-soluble delivery systems for parenteral administration of relatively insoluble parent drugs are explored. Micellar prodrugs, besides being highly water soluble, have additional advantages in that their micelles solubilize poorly soluble degradation products which may otherwise precipitate and may act as a self-stabilizing influence due to protection of the hydrolytically labile prodrug linkage within the micelle interior. Two 21-esters of methylprednisolone previously identified as having promising dilute solution stability have now been shown to self-associate in aqueous solution at higher concentrations, as determined by solubility, kinetic, and light-scattering measurements. One consequence of self-association is that free methylprednisolone, the product of prodrug hydrolysis, is solubilized in concentrated prodrug formulations. In addition, acid- and base-catalyzed hydrolysis rate constants are altered in the micelles, resulting in further prolongation of shelf life in concentrated solutions. Due to the added benefits of self-micellization, the water-soluble 21-esters investigated exhibit shelf lives exceeding 2 years at 30 degrees C, the upper limit of the controlled room temperature range.

Chemistry, Pharmaceutical↗

PubMed1985

Prediction of solubility in nonideal multicomponent systems using the UNIFAC group contribution model.

There is a need to identify suitable blends of solvents to dissolve drugs. Empirical approaches, such as trial-and-error and response surface, require several solubility measurements. In this study the UNIFAC method was used to predict solubility in highly nonideal multicomponent systems in which only the solute enthalpy of fusion and melting point must by measured. UNIFAC combines a group contribution approach with the UNIQUAC model for activity coefficients. Parameters characterizing interactions among constituent groups of a molecule have been previously determined from binary vapor pressure data. These tabulated group parameters are used to predict activity coefficients for newly synthesized compounds. These coefficients, together with the ideal solubility, permit a prediction of solubility. The solubility of 4-hexylresorcinol in ethyl acetate, ethyl myristate, and hexane mixtures was both measured and calculated using UNIFAC. The predicted solubilities were within 10% of the experimental solubilities for all but 3 of 21 mixtures. Since the method accounted for positive and negative deviations from ideality in a hydrogen-bonding system of molecules having different sizes, it shows great potential for use in pharmacy.

Acetates↗

PubMed1989

Self-association and solubility behaviors of a novel anticancer agent, brequinar sodium.

To aid in the selection of appropriate excipients to formulate brequinar sodium [6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinolinecarboxyli c acid sodium salt; DuP 785], studies were initiated to characterize thoroughly its solubility behavior. The measured solubilities at RT (approximately 23 degrees C) agreed with the theoretical values in the pH range from 0.5 to 7.2, but became significantly greater than theoretical values at pH values above 7.2. This deviation was likely due to the vertical stacking-type self-association between brequinar molecules in water. The NMR and pH methods determined a critical association concentration of 15 mg/mL. Sodium salicylate, which has been proven to interfere with molecular self-association, reduced drug solubility from 116 to 10 mg/mL. But urea, another deaggregative agent, gave about a twofold increase rather than a decrease in solubility. Addition of sodium chloride caused a 226-fold decrease in solubility. The apparent solubility product did not remain constant but decreased as sodium chloride concentration increased, suggesting that the added salt decreased the degree of self-association between brequinar molecules. Among four surfactants examined (a bile salt with a rigid fused ring versus three ordinary surfactants with a flexible chain structure), only sodium cholate significantly increased the aqueous solubility of brequinar sodium.

Antineoplastic Agents↗

PubMed1991

Influence of solute structure on deviations from the log-linear solubility equation in propylene glycol:water mixtures.

The solubilities of the methyl, ethyl, propyl, and butyl esters of p-hydroxy- and p-aminobenzoates have been determined in propylene glycol:water mixtures. The log of the observed solubility data in propylene glycol:water mixtures was examined for deviations from the following equation: In Xi = f In (Xc) + (1 - f) In (Xw), where Xi is the calculated mole fractional solubility of the solute, f is the volume fraction of cosolvent, Xc is the observed mole fractional solubility in the neat cosolvent, and Xw is the solubility in water. In each case, the deviations from the predicted solubilities demonstrated a characteristic pattern. Positive deviations were observed at high volume fractions of cosolvent, while negative deviations were observed at low volume fractions. The magnitude of the deviations at low volume fractions of cosolvent was related to the carbon chain length within each group of esters. A similar phenomenon was not observed at high volume fractions of cosolvent; however, the magnitude of the deviations was dependent on the nature of the polar group on the ester. The data are interpreted in terms of the possible effects of solvent structure on the solubility of the solutes.

Benzoates↗

PubMed1994

Hydrophobic effect at the origin of the low solubility of inert solid substances in hydrogen-bonded solvents.

The new solubility equation derived from the thermodynamics of mobile order in liquids is used to predict the solubility of four solid aliphatic and aromatic hydrocarbons, namely, tricosane, octacosane, biphenyl and pyrene, in nonassociated and hydrogen-bonded solvents. The analysis of the relative importance of the different terms contributing to the solubility shows that (1) the fluidization of the solute always represents a barrier to the solubility, (2) in non-hydrogen-bonded solvents, the solubility essentially results from the balance of the exchange entropy correction and the change in the nonspecific cohesion forces upon mixing, (3) in alcohols or in water, the solubility is mainly determined by the hydrophobic effect which corresponds to a solute rejecting effect of the solvent. This effect is responsible for the lower solubility values of the inert substances in associated solvents with respect to those in nonassociated solvents.

Chemical Phenomena↗

PubMed2004

Immunoglobulin E-reactivity of wheat-allergic subjects (baker's asthma, food allergy, wheat-dependent, exercise-induced anaphylaxis) to wheat protein fractions with different solubility and digestibility.

Baker's asthma, food allergy to wheat, and wheat-dependent, exercise-induced anaphylaxis (WDEIA) are different clinical forms of wheat allergy. We investigated the correlation of solubility and digestion stability of wheat allergens with the IgE-reactivity patterns of different patient groups. Three wheat protein fractions were extracted according to their solubility: salt-soluble albumins and globulins, ethanol-soluble gliadins, and glutenins soluble only after treatment with detergents and reducing reagents. Sera from subjects with history of each variant of wheat allergy were characterized by CAP FEIA and immunoblotting. There was a high degree of heterogeneity of recognized allergens between the different subject groups as well as within these groups. However, subjects with WDEIA showed similar immunoglobulin E (IgE)-reactivity patterns to gliadins and especially to a 65 kDa protein. Subjects with baker's asthma as well as the food-allergic subjects had the most intense IgE-reactivity to the albumin/globulin fraction. The latter group additionally showed IgE-reactivity to the other fractions. Divergent results of immunoblotting and CAP-FEIA demonstrated that the detection of wheat-specific IgE highly depends on the applied method, thus the diagnostic tool must be carefully chosen. Most wheat allergens were rapidly digested as analyzed by determination of IgE-reactivity on immunoblots to wheat extracts after simulation of gastric and duodenal digestion. However, ethanol-soluble gliadins were stable to gastric enzymes and exhibit low solubility in gastric and duodenal fluids. Therefore, they are likely to be important in food allergy to wheat.

Albumins↗

PubMed1984

Subcellular distribution and kinetic properties of soluble and particulate-associated bovine adrenal glycerol kinase.

The subcellular distribution and substrate kinetics of soluble and particulate-associated bovine adrenal glycerol kinase have been investigated. Whole adrenal, adrenal cortex and adrenal medulla were examined for distribution of glycerol kinase between soluble and particulate fractions. No major differences in distribution were noted between these tissues; of the total homogenate activity, 0-20% sedimented with the nuclear fraction, 24-36% sedimented with the post-nuclear fraction and 64-69% remained soluble. Steady-state kinetic parameters of glycerol kinase activity were compared in the soluble and mitochondrial fractions. The Km for glycerol in the soluble fraction was 6.3 +/- 0.1 microM and in the mitochondrial fraction was 4.0 +/- 0.3 microM. The Km for ATP in soluble fraction was 12.8 +/- 1.5 and in the mitochondrial fraction was 5.3 +/- 1.6. Release of adrenal glycerol kinase from the mitochondrial fraction was investigated using inorganic phosphate, ATP and glycerol 3-phosphate. Of these compounds, only ATP and glycerol 3-phosphate were effective in releasing particulate-associated glycerol kinase. Inorganic phosphate had no effect upon release. Particulate-associated glycerol kinase activity of the mitochondrial fraction was stimulated by addition of succinate and ADP and was inhibited by addition of atractyloside. The data presented here indicate that bound glycerol kinase found within the mitochondrial fraction is kinetically distinct from soluble glycerol kinase and binding to mitochondria is responsive to substrate and product levels within the physiological range.

Adenosine Triphosphate↗

PubMed1987

Differential effects of soluble and immobilized fibronectins on aortic endothelial cell proliferation and attachment.

We studied the effects of soluble and immobilized forms of plasma fibronectin on bovine aortic endothelial cell (AEC) proliferation and attachment. Soluble fibronectin stimulated AEC growth at 10 micrograms/ml, but at higher concentrations of soluble fibronectin AEC growth was progressively inhibited. The growth rates of arterial smooth muscle cells (ASMC) and dermal fibroblasts (DF) were not altered by soluble fibronectin concentrations of 10 to 100 micrograms/ml. Plasma fibronectin, immobilized by attachment to culture dish surfaces, had no significant effects on the proliferation of any of the cell types examined. The attachment rates of AEC were decreased in the presence of 50 micrograms/ml soluble fibronectin. Immobilized fibronectin increased the rate of AEC attachment, but had no significant effects on ASMC or DF attachment; however, 12 h after plating there was nearly 100% attachment in all groups, whether or not fibronectin was present in the system. That soluble and immobilized fibronectins elicit disparate cellular responses is consistent with published reports of different cell surface receptors for different forms of the protein; in this manner, cells enmeshed in an interstitial matrix containing immobilized fibronectin could still respond to soluble fibronectin in the extracellular milieu.

Animals↗

PubMed2005

Contents of soluble, cell-wall-bound and exuded phlorotannins in the brown alga Fucus vesiculosus, with implications on their ecological functions.

Phlorotannins are ubiquitous secondary metabolites in brown algae that are phenotypically plastic and suggested to have multiple ecological roles. Traditionally, phlorotannins have been quantified as total soluble phlorotannins. Here, we modify a quantification procedure to measure, for the first time, the amount of cell-wall-bound phlorotannins. We also optimize the quantification of soluble phlorotannins. We use these methods to study the responses of soluble and cell-wall-bound phlorotannin to nutrient enrichment in growing and nongrowing parts of the brown alga Fucus vesiculosus. We also examine the effects of nutrient shortage and herbivory on the rate of phlorotannin exudation. Concentrations of cell-wall-bound phlorotannins were much lower than concentrations of soluble phlorotannins; we also found that nutrient treatment over a period of 41 days affected only soluble phlorotannins. Concentrations of each phlorotannin type correlated positively between growing and nongrowing parts of individual seaweeds. However, within nongrowing thalli, soluble and cell-wall-bound phlorotannins were negatively correlated, whereas within growing thalli there was no correlation. Phlorotannins were exuded from the thallus in all treatments. Herbivory increased exudation, while a lack of nutrients had no effect on exudation. Because the amount of cell-wall-bound phlorotannins is much smaller than the amount of soluble phlorotannins, the major function of phlorotannins appears to be a secondary one.

Animals↗

PubMed2005

Impact of the amount of excess solids on apparent solubility.

PURPOSE: The impact of excess solids on the apparent solubility is examined. METHODS: The apparent solubility of some model drugs was measured in various buffered solutions, with various amounts of excess solid. To help understand the dependence of the solubility on the amount of solid, we evaluated the dissolution and crystallization rates of indomethacin (IDM), one of the model drugs, at near-equilibrium conditions. RESULTS: In the case of IDM, the apparent solubility decreased with an increase in the solid amount at pH 5 and 6. On the other hand, it increased with an increase in the solid amount at pH 6.5 and 7. The crystallization and dissolution rates of IDM decreased and increased, respectively, with an increase in pH values, and became equal at between pH 6 and 7. Therefore, the apparent solubility was most likely to be affected by the balance between the crystallization and dissolution rates. The apparent solubility of other model drugs showed the same trend, although the dependency on the solid amount was not as significant as in the case of IDM. CONCLUSIONS: The apparent solubility was affected by the amount of solid for all the model drugs investigated. This was most likely to be caused by a competition between the crystallization and dissolution rates.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2005

The effects of food on the dissolution of poorly soluble drugs in human and in model small intestinal fluids.

PURPOSE: This study was conducted to determine the effect of food on drug solubility and dissolution rate in simulated and real human intestinal fluids (HIF). METHODS: Dissolution rate obtained via the rotating disk method and saturation solubility studies were carried out in fed and fasted state HIF, fed dog (DIF), and simulated (FeSSIF) intestinal fluid for six aprotic low solubility drugs. The intestinal fluids were characterized with respect to physical-chemical characteristics and contents. RESULTS: Fed HIF provided a 3.5- to 30-times higher solubility compared to fasted HIF and FeSSIF, whereas fed DIF corresponded well (difference of less than 30%) to fed HIF. The increased solubility of food could mainly be attributed to dietary lipids and bile acids. The dissolution rate was also 2 to 7 times higher in fed HIF than fasted HIF. This was well predicted by both DIF and FeSSIF (difference of less than 30%). CONCLUSIONS: Intestinal solubility is higher in fed state compared to fasted state. However, the dissolution rate does not increase to the same extent. Dog seems to be a good model for man with respect to dissolution in the small intestine after intake of a meal, whereas FeSSIF is a poorer means of determining intestinal saturation solubility in the fed state.

Adult↗

PubMed1976

Analysis of soluble fibrin complexes by agarose gel chromatography and protamine sulfate gelation.

The molecular makeup of soluble fibrin complexes was studied by gel exclusion chromatography using radio-labelling to characterize individual components in protein mixtures. Products of limited plasmin degradation of fibrinogen and mixtures of fibrinogen and "early" fibrinogen digests formed high molecular weight soluble fibrin complexes upon incubation with thrombin. Purified, nonclottable fragment Y did not incorporate into soluble fibrin complexes, nor could we demonstrate incorporation of fragments D and E as previously described from our laboratory. Thus, under the conditions of these experiments, soluble fibrin complexes have two identifiable components, fibrin monomer and clottable fragment X monomer, although incorporation of native fibrinogen or fragment X unreacted by thrombin into soluble fibrin complexes cannot be excluded. Individual fractions of thrombin-treated early fibrinogen digests isolated by agarose gel chromatography were treated with protamine sulfate at 37 degrees C resulting in precipitation-gelation of greater than 90 per cent of high molecular weight soluble fibrin complexes; whereas, less than 10 per cent of lower molecular weight fibrinogen degradation products precipitated by protamine sulfate. These findings do not support the widely held concept that soluble fibrin complexes incorporate nonclottable degradation products of fibrinogen proteolysis, nor do they support the notion that the so-called paracoagulation reaction induced by protamine sulfate results from the splitting of complexes between fibrin monomer and nonclottable fibrinogen degradation products.

Binding Sites↗

PubMed1979

The formation and thermal stability of in vitro assembled fibrils from acid-soluble and pepsin-treated collagens.

The role of the non-helical regions of the collagen molecule in fibrillogenesis has been investigated by comparing the kinetics of fibril formation of pepsin-treated acid-soluble collagen, acid-soluble collagen and mixtures of the two and by comparison of the thermal stabilities of the fibrils formed. The acid-soluble collagen was found to aggregate more rapidly than the pepsin-treated collagen under physiological conditions of pH and ionic strength. Variations in ionic strength, at physiological pH, were found to have differing effects on the aggregation of these two forms of soluble collagen. Fibrils formed from the pepsinized-collagen had a lower thermal stability tha n those formed from the intact collagen. The behavior observed with mixtures of acid-soluble and pepsin-treated collagens was found to be quantitatively consistent with the pepsinized collagen being able to utilize the nuclei formed by the acid-soluble collagen for subsequent growth. However, the use of the acid-soluble nuclei by the pepsinized collagen for growth did not enhance its rate of precipitation during the growth phase, nor did it enhance the thermal stability of the fibrils formed from the pepsinized collagen.

Animals↗

PubMed1986

Anti-complementary action of polymorphic "solubility forms" of particulate inulin.

Inulin crystallizes in a series of polymorphic forms with different solubility rates, ranging from one instantly soluble at 23 degrees C (beta 0(23) inulin) through a form soluble at 37 degrees C with a half-time of 8 min (alpha 8(37) inulin) to a form virtually insoluble at 37 degrees C (gamma inulin). All forms are interconvertible, the more soluble and unstable progressing on standing to less soluble and more stable forms, only reversible by complete solution followed by recrystallization. The end product is the stable gamma inulin, only formed by polymers greater than 8000 mol. wt. A method is given for preparing pure "gamma inulin for injection", comprising insoluble ovoids of less than 1 micron diameter free of soluble inulin and endotoxin. An assay developed for complement action by the alternative pathway showed that gamma inulin was the most potent activator polymorph, more active than killed S. aureus and zymosan. Dissolved inulin and the more soluble polymorphs were inactive and in a mixture hindered alternative pathway activation by the gamma form.

Chromatography, DEAE-Cellulose↗

PubMed1992

Carboxypeptidase H in bovine pituitary gland: soluble forms are not processed at the C-terminus.

Carboxypeptidase H (CP-H) has been characterized in anterior and posterior lobes of bovine pituitary with regard to subcellular distribution, enzymatic properties, nature of membrane association, number of forms and C-terminal processing. Anterior lobe contained both soluble and membrane forms of CP-H with similar enzymatic properties after extraction at pH 5.5. The soluble forms represented about 70% of the total activity. Two soluble and two membrane forms, of 53 and 56 kDa, were demonstrated by immunoblotting and after purification. The amount of the 56 kDa soluble form increased with the salt content of the extraction buffer. Endoglycosidase digestions showed that the difference in size was not due to differential N-linked glycosylation and also showed that CP-H oligosaccharides do not become resistant to endoglycosidase H. CP-H in posterior lobe was also composed from about 70% soluble and 30% membrane forms. Only 53 kDa CP-H was detected in soluble and membrane fractions of posterior lobe. All forms of CP-H from both lobes reacted with antiserum directed to the C-terminus. These results do not support previous observations that soluble and membrane forms of CP-H can be distinguished by size and C-terminal processing.

Amino Acid Sequence↗

PubMed1984

The effect of cadmium on the collagen solubility of embryonic chick bone in tissue culture.

The effect of cadmium (Cd) on the solubility of bone collagen was examined in cultured tibiae from 9-day chick embryos. The solubility of collagen was not significantly increased by 8.9 microM Cd, but showed a significant increase at 13.4 microM Cd. As the [3H]hydroxyproline (Hyp) formation was inhibited by Cd at 8.9 and 13.4 microM [3H]Hyp formation and collagen solubility were investigated in the presence of 200 microM Fe2+, a metal which is known to prevent the inhibitory effects of Cd on prolyl hydroxylase in vitro. Fe affected neither a decrease in [3H]Hyp formation nor an increase in collagen solubility caused by Cd. This suggests that a Cd-induced increase in collagen solubility may be due to the decrease of lysyl oxidase activity, not to the formation of underhydroxylated collagen. Zn at 48 and 134 microM depressed the Cd-induced increase in collagen solubility, but caused no increase in collagen solubility. Our present and previous results suggest that Zn can protect the disturbance of both the collagen synthesis and the collagen cross linking caused by Cd.

Animals↗

PubMed1996

Hormone-binding and solubility properties of fusion proteins containing the ligand-binding domain of the human androgen receptor.

The ligand-binding properties of the human androgen receptor (AR) reside in the carboxy terminus of the receptor and are retained in fusion proteins encoding this domain. Despite a wealth of information pertaining to the importance of specific amino acid residues in the binding of ligands, the precise amino terminal boundary of this domain has not been determined for the androgen receptor. The current studies focused on the expression of a series of AR fusion proteins in bacteria. These experiments demonstrate that specific androgen binding is detected in a fusion protein encoding amino acid residues 675-917, although this binding is of lower affinity than that observed for the native AR. Inclusion of an additional segment (residues 622-675) restores the capacity of the hormone-binding domain to bind mibolerone with high affinity. Detailed studies of the ligand-binding properties and solubility of one AR fusion protein (625-917) indicate that although the levels of ligand binding and soluble receptor fusion protein usually vary in parallel, this is not true at all time points and the proportion of soluble AR fusion that is able to bind hormone is highest when the levels of soluble AR fusion protein are lowest. This observation, coupled with the changes in the quantity of soluble and insoluble fusion protein occurring at different times following induction at 12 degrees C, 22 degrees C, and 37 degrees C, suggests that the saturation of one or more steps is required for folding of the AR hormone-binding domain to a conformation that is both soluble and competent to bind hormone under conditions of high-level expression. Analysis of the solubility of six different fusion proteins containing different portions of the AR hormone-binding domain suggests that a discrete segment of this domain is not responsible for its synthesis as predominantly insoluble aggregates in bacteria when expressed at high levels.

Base Sequence↗

PubMed2004

Hydroxyapatite solubility in simple inorganic solutions.

OBJECTIVE: To use solid titration and laser-scattering end-point detection to determine the hydroxyapatite (HAP) solubility isotherm at 37 degrees C in a plain KCl solution, with CO(2) present, and with additional phosphate. DESIGN: Pulverised HAP solid was used to perform a titration to saturation. A very sensitive detector capable of detecting the light scattered at small forward angles from a laser beam was adopted to monitor the onset of precipitation (or failure to dissolve) near the equilibrium point. Each addition of HAP solid caused a step increase in scattered light and this signal decreased quasi-exponentially with time. When a steady but elevated scattering was obtained, small portions of 1M HCl were added to lower the pH by about 0.5-2 units, according to need, to dissolve excess solid and allow a further titration. The scatter signal and pH data, plotted against the amount of HAP added, were used to estimate the actual end-point by interpolation and thus construct each point on the solubility isotherm. RESULTS: The solubility isotherm for HAP in plain KCl solution in the absence of CO(2) obtained now differs substantially from the results of previous solubility studies (i.e. much lower). The increase in solubility due to CO(2) reported earlier was confirmed, while the effect of excess phosphate was found to be to increase the apparent solubility of HAP, contrary to elementary mass-action expectations. CONCLUSIONS: The solid titration method is a more reliable approach than that of conventional excess solid method with respect to the determination of the HAP-carrying capacity. The solubility of HAP appears to be substantially lower than previously reported, and a reconsideration of all aspects of the system is warranted.

Biocompatible Materials↗