Water Solubility Characteristics Research Articles

Prediction of Solubility and Permeability Class Membership: Provisional BCS Classification of the World’s Top Oral Drugs

The Biopharmaceutics Classification System (BCS) categorizes drugs into one of four biopharmaceutical classes according to their water solubility and membrane permeability characteristics and broadly allows the prediction of the rate-limiting step in the intestinal absorption process following oral administration. Since its introduction in 1995, the BCS has generated remarkable impact on the global pharmaceutical sciences arena, in drug discovery, development, and regulation, and extensive validation/discussion/extension of the BCS is continuously published in the literature. The BCS has been effectively implanted by drug regulatory agencies around the world in setting bioavailability/bioequivalence standards for immediate-release (IR) oral drug product approval. In this review, we describe the BCS scientific framework and impact on regulatory practice of oral drug products and review the provisional BCS classification of the top drugs on the global market. The Biopharmaceutical Drug Disposition Classification System and its association with the BCS are discussed as well. One notable finding of the provisional BCS classification is that the clinical performance of the majority of approved IR oral drug products essential for human health can be assured with an in vitro dissolution test, rather than empirical in vivo human studies.

Effect of temperature on water sorption and solubility of dental adhesive resins

Objective This study examined the effect of temperature on water sorption and solubility characteristics of four commercial dental adhesives. The null hypothesis tested was that temperature has no effect on the water sorption and solubility characteristics of these adhesives. Methods The tested materials were: three-step etch-and-rinse (All-Bond 2, AB), two-step etch-and-rinse (One-Step, OS), two-step self-etch (Clearfil SE Bond, SE) and one-step self-etch (Clearfil S3 Bond, S3) adhesives. Seven resin disks (6 mm in diameter × 1 mm in thickness) were prepared from each tested material and were stored in deionized water at 23 °C, 37 °C and 55 °C. Water sorption and solubility of the resin disks were measured before and after water immersion and desiccation following two consecutive sorption and desorption cycles. The water sorption and solubility values obtained were analyzed using two-way ANOVA and Tukey's multiple comparison tests. The relationships between maximum water sorption, solubility and kinetics of water diffusion with temperature were evaluated by means of Pearson correlation statistic. Results OS exhibited the highest water sorption and solubility values in the second sorption–desorption cycle at 55 °C ( p < 0.001). This is followed by S3, SE and AB with no significant difference between SE and AB. Significant positive correlations were observed between maximum water sorption ( r = 0.307, p < 0.01), solubility ( r = 0.244, p < 0.05), water sorption ( r = 0.651, p < 0.001) and desorption ( r = 0.733, p < 0.001) diffusion coefficients (obtained using Fick's law of diffusion) with temperature in the second cycle. Significance High temperatures increased water sorption of simplified adhesives. Such water sorption may contribute to the failure of resin–dentin bonds.

Preparation and properties of microfibrillated cellulose polyvinyl alcohol composite materials

Abstract This work reports the preparation of MFC–PVA composite films, and the thermal and mechanical properties of these films. Microfibrillated cellulose (MFC), which was separated from kraft pulp by a mechanical process, was used as the reinforcement in polyvinyl alcohol (PVA) matrix. This MFC reinforcement has an interconnected web-like structure with fibrils having a diameter in the range of 10–100 nm, as observed by TEM. MFC–PVA composite films were created by casting from a water suspension to produce a homogeneous dispersion of MFC in the polymer matrix. DMA shows an increase of the storage modulus in the glassy state with increasing MFC content, but a more significant increase in modulus is detectable above the glass transition temperature. There is a steady increase in both the modulus and strength of the composite films until a plateau is reached at 10 wt% MFC. The thermal stability of the PVA composite films is slightly increased with the addition of MFC. As a result of this research, it has been shown that MFC is an excellent reinforcement comparable to cellulose nanowhiskers. Furthermore, by combining MFC with PVA in addition to good mechanical properties, this composite has good chemical resistance and biodegradability. The water soluble characteristics of PVA combined with a water dispersion of MFC are also easily processable.

Optimization of edible whey protein films containing preservatives for water vapor permeability, water solubility and sensory characteristics

The effect of protein, sorbitol, beeswax and potassium sorbate concentrations in whey protein films on their water vapor permeability, water solubility and organoleptic properties was investigated using mixture response surface methods. All factors including protein, sorbitol, beeswax and potassium sorbate influenced water vapor permeability and water solubility of the films. Beeswax was the most important factor influencing the stickiness and appearance of the films. Amount of protein (50–65%, w/w) had no effect on stickiness and appearance, while the amount of sorbitol (35–50%, w/w) in the films had no influence on appearance. Mixture proportions of protein = 0.53, sorbitol = 0.38, beeswax = 0.08 and potassium sorbate = 0.01 would yield an edible film with minimum stickiness, water vapor permeability ⩽ 9 g mm m −2 h −1 kPa −1, water solubility ⩾ 39% and appearance score ⩾ 80.

Water Sorption and Solubility of Methacrylate Resin–based Root Canal Sealers

The water sorption and solubility characteristics of three contemporary methacrylate resin-based endodontic sealers, EndoREZ, Epiphany, and InnoEndo, were compared with those obtained from Kerr EWT, Ketac-Endo (positive control), GuttaFlow, and AH Plus (both negative controls). Ten disks of each material were dehydrated in Drierite for 24 h and weighed to constant dry mass. They were placed in water and weighed periodically until maximum water sorption was obtained. The disks were dehydrated again to determine their mass loss (solubility) at equilibrium. Epiphany exhibited the highest apparent water sorption (8%) followed by Ketac-Endo (6.2%), InnoEndo (3.4%), EndoREZ (3.0%), AH Plus (1.1%), GuttaFlow (0.4%), and Kerr EWT (0.3%). Significantly higher solubility (3.5-4%) were observed for all three methacrylate resin-based sealers and Kerr EWT (3.95%), compared with Ketac-Endo (1.6%), AH Plus (0.16%), and GuttaFlow (0.13%). American Dental Association specifications require<3% solubility for endodontic sealers. Only Ketac-Endo, AH Plus, and GuttaFlow met that criterion.

Lipid-Lowering Effect of Hot Water-Soluble Extracts ofSaururus chinensisBail on Rats Fed High Fat Diets

We evaluated the inhibition of low-density lipoprotein (LDL) oxidation inhibition by a hot water-soluble extract of Saururus chinensis Bail (HWSCB) in vitro and the lipid-lowering effects of HWSCB in rats fed high fat diet (HFD). HFDs were supplemented with 5% HWSCB (HFSCB5 group), 10% HWSCB (HFSCB10 group), or 1% tannic acid (Tannin group). The Tannin group served as a positive control for the study, based on tannic acid's known lipid-lowering effect and water-soluble characteristics. LDL oxidation was dose-dependently inhibited in the presence of HWSCB, and the effect of HWSCB was comparable to that of vitamin C. Significant reductions in triglyceride (P < .05) and cholesterol (P < .05) levels in the plasma and liver of the HFSCB5, HFSCB10, and Tannin groups were observed. High-density lipoprotein cholesterol was elevated (P < .05), but LDL was decreased in a dose-dependent manner for the HFSCB samples. These results were associated with a significant decrease in the atherogenic index for the HFSCB samples, especially for HFSCB10. In addition, fecal excretion of triglyceride with HWSCB supplementation was greater than with tannic acid supplementation. The findings of this study suggest that HWSCB may reduce plasma and hepatic lipids, especially triglyceride, in rats fed high fat diet.

Development of a Novel Slow-Releasing Iron−Manganese Fertilizer Compound

Development of a new slow-release micronutrient fertilizer of iron−manganese is described. Studies include formulation, synthesis, kinetics, characterization, and testing. The compound is a partially polymerized, iron−manganese−magnesium polyphosphate, which is produced at 200 °C by reaction of iron, manganese, and magnesium oxides with phosphoric acid, followed by neutralization to pH 5.6. Polymerization is optimal at 21.2% with an Fe/Mn/Mg/P molar ratio of 1:0.51:1.15:7.33. Condensation kinetics show multistage processes with plateau formation at the end of each stage. The compound is crystalline with new XRD patterns indicative of a regular arrangement of polyphosphate chains. ESR spectra reveal Mn predominantly in the IV state. The product has ideal slow-release characteristics of low water solubility but high citrate and DTPA solubility, indicating high bio-availability of the micronutrients. Plant trials with chilli show a 45.6% increase in yield, at Fe 2 kg/ha−Mn 1 kg/ha as the slow-release fertili...

Characteristics of Gastrointestinal Absorption of DX-9065a, a New Synthetic Anticoagulant

DX-9065a, a newly synthesized anticoagulant that selectively inhibits factor Xa, is a zwitterion and has characteristics of high water solubility and low lipophilicity. We predicted the fraction absorbed (Fa) of DX-9065a to be approximately 15-35% in humans, based on the boundary layer theory using the intestinal perfusion method in rats. However, human oral bioavailability was 2-3% in clinical trials, and the result of actual human bioavailability was lower than that of the predicted Fa. Thus, in this report, the reason for low oral bioavailability of DX-9065a was examined by in vitro and in vivo experiments. The factors affecting oral bioavailability of DX-9065a were not the hepatic first-pass effect, degradation of the drug in intestinal fluid, nor the interaction of the drug with the intestinal mucin. Furthermore, no effect of P-gp efflux was observed. Oral absorption of the drug in rats with bile duct ligation was significantly higher than that in normal rats with bioavailability of 17 and 3%, respectively. It was confirmed that bile acids inhibited DX-9065a absorption because DX-9065a interacted with bile acids to form insoluble complexes. The results suggest that the complex formation of DX-9065a with bile acids in the intestinal tract is an important factor affecting absorption of DX-9065a.

Effect of resin hydrophilicity and temperature on water sorption of dental adhesive resins

This study examined the effects of copolymer hydrophilicity and temperature on water sorption and solubility characteristics of five copolymer blends of increasing degree of hydrophilicity using gravimetric measurements. Six resin disks (15 mm in diameter×1 mm in thickness) were prepared from each copolymer blend and were stored in deionised water at 23, 37 and 55 °C. Water sorption and solubility of the resin disks were measured before and after water immersion and desiccation. Multiple regression analysis of water sorption was performed on two independent variables, copolymer hydrophilicity and temperature. Maximum water sorption increased significantly with Hoy's total cohesive energy density ( δ t ), Hoy's solubility parameter for polar forces ( δ p ) and hydrogen bonding ( δ h ), but was not influenced by temperature. However, a significant positive relationship was observed between diffusion coefficients (obtained using Fick's law of diffusion) and temperature. The water absorption activation energy was 10 kJ/mol for the most hydrophilic copolymer blend R5 and 35–51 kJ/mol for copolymer blends R1–R4. The positive relationship between maximum water uptake and copolymer hydrophilicity suggests that water molecules diffuse through the polymer matrices by binding successively to the polar sites via hydrogen bonding. Such water sorption may determine the durability of resin–dentine bonds.

Water-soluble characteristics of chlorine in char derived from municipal solid wastes

Chlorine in char derived from municipal solid waste (MSW) was characterized and quantified based on its water solubility: easily water-soluble, hardly water-soluble, and non-water-soluble chlorine. For that, a four-cycle process of water-washing, heating or carbonation were carried out. In order to confirm the characteristics of non-water-soluble chlorine, additional thermal treatment and an alkali–acid washing process were applied to washed char. It was found that a large particle size of char (0.5–1.0 mm) significantly contributed to the amount of non-water-soluble chlorine. Pulverization and HNO 3–HF digestion were performed to identify a factor to interfere chlorine release from char with a large particle size. Pulverization was proven ineffective for release of non-water-soluble chlorine, whereas approximately 32% of non-water-soluble chlorine was extracted by HNO 3–HF digestion. Therefore, the presence of non-water-soluble chlorine is likely to originate from its chemical property rather than simply from its physical one.

Red clover isoflavonoids as anthocyanin color enhancing agents in muscadine wine and juice

Isoflavonoid extracts from red clover ( Trifolium pratense) leaves were found to enhance overall color and stability of anthocyanin 3,5-diglucosides present in muscadine grape ( Vitis rotundifolia) juice and wine through intermolecular copigmentation reactions. Predominant isoflavonoids present in red clover included formononetin, biochanin A, and prunetin and were the major polyphenolics identified to influence anthocyanin color and stability. Since red clover isoflavonoids have poor water solubility characteristics, this allowed for removal of extraneous non-isoflavonoid compounds using hot water and subsequent extraction with ethanol. Isoflavonoid solubility was evaluated as a function of ethanol concentration with recoveries up to 57% found in 20% solutions. Changes in maximum absorbance, total soluble phenolics, isoflavonoids, and anthocyanins were evaluated in muscadine juice and wine following the addition of isoflavonoid extracts with maximum color enhancement found at an anthocyanin to cofactor ratio of 1:8, after which their solubility was prohibitive. Additionally, dried leaves and ethanolic extracts of red clover were added prior to and following fermentation of muscadine wine (11% ethanol) stimulating the natural copigmentation that takes place during red wine fermentation and aging processes. Once fermentation was complete, finished wines were evaluated over a 9-week storage period at 20 and 37 °C. Despite low levels of isoflavonoids present, color improvement and anthocyanin stability was observed in the wines during storage. Little information is available on copigmentation reactions occurring in actual food systems, yet red clover isoflavonoids proved to be novel and effective color enhancing compounds when used in low concentrations in young muscadine wines.

Regioselective synthesis of cyclodextrin mono-substituted conjugates of non-steroidal anti-inflammatory drugs at C-2 secondary hydroxyl by protease in non-aqueous media

Three β-cyclodextrin (β-CD) conjugates of non-steroidal anti-inflammatory drugs were synthesized by enzymatic methods. Transesterification of β-CD with vinyl ester of indomethacin, ketoprofen and etodolac was performed by the catalysis of alkaline protease from Bacillus subtilis in anhydrous DMF for 3days. The drug molecules were selectively conjugated onto one of the secondary hydroxyl groups of β-CD through ester-linkage to improve their poor water solubility and absorption characteristics. The products were characterized by ESI-MS, 1H NMR and 13C NMR. The structures of products with monoacylation occurring at the C-2 secondary hydroxyl groups of β-CD were confirmed.

Syntheses of Regioisomerically Pure 5‐ or 6‐Halogenated Fluoresceins.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Syntheses of regioisomerically pure 5- or 6-halogenated fluoresceins.

Three routes to regioisomerically pure 5- and 6-iodofluoresceins or 5- and 6-bromofluoresceins are described. The first, shown in Scheme 1, involves diazotization/iodination of the corresponding aminofluoresceins. In the second approach (Scheme 2) a mixture of regioisomeric fluoresceins was prepared, and the 5-bromo isomers were isolated as the ring closed diacetates 9b and 11 by fractional crystallization. Scheme 3 shows an approach to sulfonic acid derivatives 3 and 4 of 5-iodofluorescein. This is the most convenient procedure of the three, and it is particularly useful as sulfofluoresceins have more favorable water solubility characteristics than fluoresceins that lack the sulfonic acid group.

Microbial degradation of low rank coals

The strain of Pseudomonas putida was tested in terms of the degradation ability of organic matter of lignites and subbituminous coals. The conversion degree to water soluble products and structural characteristics of bioextracts and bioresidues by elemental analysis and infrared spectroscopy were assessed. Oxidizing pretreatment with nitric acid essentially enhanced the biodegradability resulting in ∼90% solubilization of lignites and ∼40% of subbituminous coals. The bioextracts precipitated from supernatants were solids of high contribution 40–70% of oxygen functionalities and increased nitrogen content. The extent of bioresidue organic matter alteration increased with conversion depth. The enhanced hydrogen content was most characteristic feature of the residues.

Synthesis of substituted 5[ H]phenanthridin-6-ones as potent poly(ADP-ribose)polymerase-1 (PARP1) inhibitors

1-, 2-, 3-, 4-, 8-, or 10-Substituted 5( H)phenanthridin-6-ones were synthesized and found to be potent PARP1 inhibitors. Among the 28 compounds prepared, some showed not only low IC 50 values (compound 1b, 10 nM) but also desirable water solubility characteristics. These properties, which are superior to the common PARP1 inhibitors such as benzamides and isoquinolin-1-ones, are essential for potential therapeutic usage. The variety of compounds allows SAR analysis of favored substituents and substituted positions on 5( H)phenanthridin-6-one ring.

Improvement of Schwann cell attachment and proliferation on modified hyaluronic acid strands by polylysine.

Hyaluronic acid (HyA) has the intrinsic ability to promote cell proliferation and reduce scar formation. However, the clinical use of HyA has so far been limited because of its water solubility and nonadhesive characteristics. Increasing interest in HyA as a clinically useful biomaterial has prompted our study of altering HyA's physical properties to render it a potential component of nerve grafts. In this study, strands of HyA were cross-linked by glutaraldehyde (Glut), coated with polylysine, and then inoculated with Schwann cells (SCs). Results in vivo and in vitro demonstrated that cross-linked HyA strands were water insoluble and thus less biodegradable. Poly-D-lysine-resurfaced strands showed significant SC attachment of 350-400 cells/mm(2), compared to uncoated controls (0-10 cells/mm(2), p < 0.01). Fibroblast control groups showed an attachment of 40-100 cells/mm(2) on coated strands. Immunostaining for proliferating cells showed SCs as and fibroblasts as +. Cells neither adhered to nor proliferated on the modified HyA strands that were not resurfaced. The results suggest that polylysine promotes SC attachment and proliferation to glutaraldehyde-cross-linked HyA strands, the product being a three-dimensional composite with low solubility that may have potential application in nerve grafts.

Construction of Water-Soluble Phosphines, New Advances in Aqueous Organometallic Chemistry

Interest in aqueous organometallic chemistry stems from the fact that water-soluble transition metal compounds have found applications as catalysts in commercially-viable industrial processes for bulk and fine chemicals synthesis and also for their continued utility in biomedicine. As a solvent, water is unique because it displays polar and protic properties. The strong propensity of water to involve in hydrogen bonding interactions and its ability to act as a donor ligand to transition metals makes it even more unique, non-toxic and environmentally-benign, medium for chemical and biological use. In order to make the best use of some of the properties of water as a solvent, it is important that the transition metal complexes exhibit high solubility and good kinetic stability (in some instances) in water. Traditionally, phosphines functionalized with charged/polar substituants (e.g. -SO3H, -COOH or -OH) have been used as ligands to produce aqueous-soluble transition metal complexes. Recently, studies in our laboratories have demonstrated that a new generation of hydroxymethyl-functionalized bis, tris and tetradentate phosphines, upon complexation with the early and late transition metals, produce transition metal complexes possessing water-soluble characteristics. In this presentation, the design and development of water-soluble hydroxymethyl-functionalized phosphines and their application in the development of aqueous-organometallic chemistry will be discussed.

Bioavailability and biodegradation kinetics protocol for organic pollutant compounds to achieve environmentally acceptable endpoints during bioremediation.

This paper is an extension of our previous studies on quantitating biodegradation kinetics in soil slurry and compacted soil systems. Previous studies had mainly used phenol as a test contaminant. Phenol represents hydrophilic compounds which exhibit high water solubility and low soil sorption characteristics. This paper extends the experimental protocol using polycyclic aromatic hydrocarbons (PAHs) as the test contaminants. PAHs are hydrophobic compounds with low water solubility and exhibit significant partitioning in soil organic carbon. Degradation rates of PAHs are much slower, thereby requiring acclimation of indigenous soil microbiota using microcosm reactors. The experimental protocol, elaborated in this paper, results in the measurement of biokinetic parameters which can be used to quantitate both ex situ and in situ bioremediation rates and assess the attainable endpoints. Biodegradation studies were conducted for naphthalene using soil slurry, soil wafer, and soil column reactors. Microcosm reactors were set-up to acclimate soil microbiota, and carbon dioxide evolution was used as a measure of acclimation. It was found that reasonable degree of PAH acclimation was achieved after 250 days of microcosm operation. Abiotic adsorption/desorption studies showed that equilibrium was achieved in about 20 hours and approximately 45% of the initial amount of naphthalene is adsorbed by the time equilibrium is attained. Further, desorption was much slower than adsorption with equilibrium being attained in 40 hours. Biokinetic parameters were derived from the cumulative oxygen uptake data of soil slurry, wafer, and column reactors using detailed mathematical models. The cumulative oxygen uptake in all three reactors were almost the same, since naphthalene primarily degraded in the soil phase and the extent of degradation in the aqueous phase was small.

The effects of cross-linking agents on the water sorption and solubility characteristics of denture base resin.

Six different cross-linking agents were added to the monomer component of an autopolymerizing denture base resin, and their effects on the water sorption and solubility were investigated. The results of this study suggested that the chemical nature of the polymer versus that of the water molecule directly affected the water sorption of denture base resin. The addition of a cross-linking agent decreased the solubility with increasing concentration.