Water-soluble Additives Research Articles

Ibuprofen crystals with optimized properties

The common analgesic drug ibuprofen shows bad dissolution and tableting behavior due to its hydrophobic structure. Additionally its high cohaesivity results in low flowability. Because of the bad compaction behavior ibuprofen has to be granulated usually before tableting. Another problem in manufacturing is the high tendency for sticking to the punches. A crystal form with optimized properties of ibuprofen was prepared and characterized in this study. Crystallization was carried out using the solvent change technique in the presence of different water-soluble additives. These additives were only present during the crystallization process and removed after precipitation by a washing process. A nearly pure ibuprofen powder was received, as GC-analysis showed. Plate-shaped crystals with increased powder dissolution, increased flowability and good tableting behavior were obtained. All crystals were determined as isomorphic by DSC and X-ray analysis. Thus the improvement of the substance characteristics of ibuprofen is reached by changes in the outer appearance of the crystals and in surface modifications. Due to the fact that ibuprofen molecules can form hydrogen bonds, additives that can interact with these hydrogen bonds during the crystallization process can modify the properties of the resulting crystals.

Study of the tribological behavior of S-(carboxylpropyl)- N-dialkyl dithiocarbamic acid as additives in water-based fluid

There has been a growing concern for the use of water-based fluids because of the worldwide interest in environmental issues. This has promoted the research and use of water-soluble additives as environmental friendly lubricants. A kind of potential water-soluble additive, S-(carboxylpropyl)- N-dialkyl dithiocarbamic acid was prepared in this work. The friction and wear behaviors of the synthesized compounds as an additive in water-based liquid were evaluated with a four-ball tester and a ring-on-block rig. The wear scar morphology of the ball and the chemical nature of the antiwear films generated on the steel counter face were investigated with scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). It was found that the synthesized additives had excellent antiwear, load-carrying and extreme pressure performance. The additive reacted with the counter-face metal and generated a surface protective film consisting of FeS, FeS 2, FeSO 4 and an absorbed compound containing N and acid.

Influence of Type and Level of Water-Soluble Additives on Drug Release and Surface and Mechanical Properties of Surelease® Films

Ethylcellulose in combination with water-soluble additives has been used in the development of microporous membrane-coated dosage forms. In the present study, application of three types of water-soluble additives, namely polyethylene glycols (PEG 400, 3350, and 8000), maltodextrins (Maltrin M150, M100, and M040 in the order of lower to higher average polymer size and molecular weight; dextrose equivalence 16.9, 11.1, and 4.8, respectively), and xylitol, as porosity modifiers in the films of a commercially available aqueous ethylcellulose dispersion (Surelease/E-7-7060 plasticized with glyceryl tricaprylate/caprate) was investigated. The effect of type and level of these additives on drug release characteristics and surface and mechanical properties of the polymeric films was studied. Each additive was incorporated at 20 and 30% levels in the polymeric dispersion based on its solids content. Ibuprofen tablets were coated using the polymeric dispersion with and without additive at 3% w/w coat level in a fluid-bed equipment. The coated tablets were evaluated for their drug release rate, coat reflectivity (gloss), Brinell hardness, and elastic modulus. Differential scanning calorimetric analysis of the films was performed to determine the physico-chemical changes in the applied film-coats. The rate of drug release, hence film porosity, was observed to be dependent on the type and level of the additive added. The molecular weight of the additive and its concentration in the polymeric dispersion had significant influence on the rate of drug release, hardness, and elasticity of the film-coats.

Tribochemical investigation of tungsten carbide/titanium alloy tribo-couples under aqueous lubrication

The present paper deals with the fundamental understanding on the tribochemical mechanism of tungsten carbide (WC) coating and titanium alloy tribo-couples system. The tribological experiments were performed with a Timken-type tester. Water containing water-soluble additives was employed as the lubricating media. The rubbed surfaces of the carbide coating were characterized with scanning electric microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Significant titanium transfer was observed. Results of XPS analyses show that the interfacial layers formed consist of multiple oxides which suggests that oxidative reactions predominate in frictional processes under aqueous lubrication. It is proposed that the oxide layer is responsible for the tribological behavior because it controls the diffusive and adhesive wear.

Membrane Filtration Studies of Inversely Soluble Model Metalworking Fluids

Model metalworking fluids, characterized by phase separation of functional components at elevated temperatures, were studied. Results of membrane filtration experiments with three oils of differing chemical nature confirm the feasibility of specific removal of finely dispersed contaminant oils without the simultaneous loss of active components from adequately formulated fluids. Prerequisites are that membrane materials and pore sizes be suitably chosen and that operating temperatures be kept below the cloud point of the least soluble component. The most suitable filter in the present study was a hydrophilic regenerated cellulose membrane with a NMWL of 100,000 dalton. Complete oil removal was attained if membrane pore sizes did not exceed 0.1 μm. It was also found that intrinsically water-soluble boundary lubricants of the polyglycol ether type are retained by membranes in the presence of PPG-1800, which serves as a precipitation promoter above the cloud point. This is of considerable practical importance since it offers the possibility of designing water-soluble boundary lubrication and extreme pressure additives which are activated by the presence of a inversely soluble component above its cloud point. The latter compound also acts as the principal hydrodynamic lubricant of the present model formulations. The usefulness of a new analytical tool for the rapid acquisition and imaging of data pertinent to changes in molecular aggregation and phase conditions was demonstrated.

Characterization of poly(dimethylacrylamide) and the combination of poly(vinyl alcohol) and cetyltrimethylammonium bromide as dynamic electroosmotic flow suppression agents in capillary electrophoresis

Methods that allow reduction of the electroosmotic flow (EOF) to a negligible value in a simple and reproducible manner are of great interest for many potential applications in capillary electrophoresis. In the absence of an EOF the apparent mobility is equal to the effective mobility, making possible identification on the basis of literature values of mobility. In the present work we characterize two dynamic coatings based on the addition of water soluble additives to the running buffer (i) poly(dimethylacrylamide) and (ii) a combination of poly(vinyl alcohol) and cetyltrimethylammonium bromide. The performances of the two systems are evaluated under different experimental conditions.

Controlled release of U-86983 from double-layer biodegradable matrices: effect of additives on release mechanism and kinetics

Effects of additives on the drug release kinetics from biodegradable matrices is an important determinant in designing a drug delivery system. These experiments introduced the influence of an array of additives on the drug release from double-layered poly(lactic-co-glycolic acid) (PLGA) matrices. Various additives such as l-tartaric acid dimethyl ester (DMT), Pluronic® F127 (F127); 2-hydroxypropyl derivative of β-cyclodextrin (HPB), methyl derivative of β-cyclodextrin (MMB) and Beeswax (Wax), differing in molecular size, hydrophilicity and steric configuration were selected for this study. An antiproliferative 2-aminochromone, U-86983 (U-86, Pharmacia and Upjohn), was used as a model agent because of our interest in investigating local drug delivery systems for the inhibition of restenosis. The in vitro release of U-86 from PLGA matrices without additive showed a typical biphasic release kinetics, i.e. a slow diffusion release (Phase I) followed by a fast erosion-mediated release (Phase II). The water-soluble additives in PLGA matrices changed the biphasic release pattern to a near monophasic profile by increasing the release rate of the Phase I. Increasing the ratio of additives to PLGA in matrices causes a significant increase in the U-86 release rates. The high molecular weight water-soluble additive, Pluronic® F127, resulted in a matrix showing perfect zero-order release kinetics. The water-soluble cyclodextrin derivative, HPB, gave the highest release rate among all the matrices formulated. A hydrophobic additive, Beeswax, however showed biphasic release kinetics comparable to PLGA control matrices, but delayed the onset of the Phase II by 4 days. The U-86 release profiles were in good agreement with the mass loss profiles of these matrices except for the matrices with F127 and HPB additives. The morphologic evaluation of matrices using scanning electron microscopy indicates that the water-soluble additives are leachable and thus generate a highly porous structure in the matrices. The matrix pore configuration (e.g. interconnected or closed) created with different additives determined the mechanism of drug release kinetics from the various matrix formulations. In conclusion, the feasibility of modulating release rates and kinetics of an agent from PLGA monolithic matrices by utilizing various types of additives is demonstrated. Water-solubility, molecular size and steric configuration of the additives are the important determinants in generating various types of pore structures in polymer matrix which in turn affect the release mechanism and release kinetics.

Release of taxol from poly( ϵ-caprolactone) pastes: effect of water-soluble additives

We have developed a taxol-loaded polymeric surgical paste for application at tumor resection sites. The paste vehicle is based on poly( ϵ-caprolactone) (PCL), a low melting, biodegradable, biocompatible polymer containing dispersed water-soluble additives. Following gentle heating to between 44–56°C, the paste can be applied in the molten state from a syringe to tumor resection sites. Taxol/additives were co-precipitated, pulverized and incorporated into molten low molecular weight PCL. The taxol/additive/PCL composite was characterized using swelling in water, drug release into phosphate buffered saline (pH 7.4) at 37°C and scanning electron microscopic studies on samples suspended in water. In vivo drug release and anti-angiogenic activity of the composites were evaluated using the chick chorioallantoic membrane (CAM) assay. In addition, in vivo efficacy was investigated using a subcutaneous tumor in mice. The in vitro release of taxol from PCL was increased by the addition of water-soluble agents. Taxol released from the matrix inhibited angiogenesis in the CAM model and caused a mean tumor regression of about 63% in a mice tumor model.

Designed additives for controlled growth of crystals of phospholipid interacting proteins: Short chain phospholipids

A new approach to crystallization of proteins that interact with lipids has been applied to the protein crambin. Short chain phospholipids are water-soluble additives and effectively lower the amount of protein needed to form crambin crystals by lowering protein solubility and inhibiting crystal growth in the fastest growing direction. Compared with optimal crystallization conditions without phospholipid, which gave large crambin crystals (1.5 × 0.7 × 0.5 mm), a 30–60-fold decrease in protein concentration as well as 5-fold decrease in volume were achieved. As a result, the efficiency of crystal production was increased by 150–300-fold. The crystals obtained diffracted beyond 1.5 Å resolution. The most effective additive, phosphotidylcholine, had a size comparable to the proposed binding site on crambin and on the homologous membrane-active toxins. The procedure developed may be useful for crystallization of other phospholipid interacting proteins as well as transmembrane proteins.

Studies on permeation through polymer latex films, III. Modification using soluble polymeric additives

AbstractThe influence of two distinct types of water leachable polymeric additives upon the transport properties across polymer latex films is considered. Hydroxypropyl methylcellulose, added as an aqueous solution, and a methyl methacrylate–methacrylic acid copolymer, added as latex particles, are both shown to be more effective than lower molecular weight rapidly water soluble additives, typified by sucrose, in enhancing solute transport and creating pathways for convective diffusion.

Plastic shaping of aqueous alumina suspensions with sucrose and maltodextrin additives

Traditional methods for the shape-forming of engineering ceramics entail plastic deformation of powder slurries containing hazardous organic liquids as suspending media. Replacing these organic with aqueous media requires the development of environmentally benign, water-soluble additives which serve as plasticizers and binders. Fundamental studies were performed with aqueous suspensions of colloidalα-Al2O3 to evaluate the role of sucrose and maltodextrin on viscosity, sedimentation, and filtration characteristics, plastic flow behavior of filter cakes, and sinterability. Maltodextrin systems exhibited superior results, including filtration to high packing densities and clay-like plasticity with minimal cracking.

Soluble gas injection for waterflood profile modification

Abstract A method involving the addition of water-soluble gas to exploit relative permeability relationships is evaluated for its potential to modify a waterflood profile. In this process, a soluble gas is added to injected water in an amount such that a single-phase aqueous solution enters the formation; however, the bubble point pressure is crossed in the steeply varying pressure profile around an injector. Solution gas alters the relative permeability to water in those zones taking water. Thus, the current water injection profile transports profile modification agent to the zones which need it most. Analytical model results for the radial flow of dissolved gas and subsequent gas evolution indicate that gas saturation is partitioned according to the permeability-porosity ratio. For most cases, this results in beneficial profile modification by three-phase relative permeability effects. Relative permeability reduction by a factor of three is anticipated through the nucleation of a trapped gas saturation. Gas saturations accumulate with time, making the process more beneficial with continued implementation. Though initially this process yields a near-wellbore treatment, prolonged application produces a trapped gas zone deep into the reservoir. Gas evolution away from the injector aids in injectivity maintenance. Increase in microscopic displacement efficiency, in addition to volumetric sweep, is also expected. Nitrogen, methane, and carbon dioxide are screened as potential water-soluble additives.

Orientation of Enzyme Catalysis and Specificity by Water-Soluble Additives

Orientation of Enzyme Catalysis and Specificity by Water-Soluble Additives

Modification of the pore structure of sol-gel-derived ceramic oxide powders by water-soluble additives

Aqueous alumina and zirconia sols have been prepared from pseudoboehmite and zirconium carbonate powders and, together with a silica sol, were doped with water-soluble additives, namely a silicone glycol copolymer, a polyvinyl alcohol and oxalic acid. Gel powders, which were obtained on dehydration of the doped sols, were calcined at 973 K to oxides. The latter powders were characterised by nitrogen isotherms and mercury porosimetry. Specific surface areas for sol-gel oxides were in the range 14–159 m 2 g −1, depending on the amount of copolymer, polyvinyl alcohol and oxalic acid in the sols. Additives narrowed the pore-size distribution and produced pore radii in the range 5–80 nm with the majority of radii between 5 and 20 nm. The controlled pore structure of sol-gel oxides which can be achieved with water-soluble additives has potential applications in advanced ceramic activities that require tailored porosities, for example, inorganic membranes.

Modifying In-Situ Combustion Performance by the Use of Water-Soluble Additives

Summary Experiments were performed to study the effects of various additives on the oxidation kinetics of Californian and Venezuelan oils. Aqueous solutions of 10 metallic salts were mixed with sand and Huntington Beach, CA, oil. The mixtures were subjected to a constant flow of air and a linear heating schedule while the effluent gases were analyzed for composition. The variation in the oxygen consumption was analyzed with a model of three competing oxidation reactions. Values for the important kinetic parameters for the three reactions were obtained for each additive. Iron and tin salts were found to enhance fuel formation, while copper, nickel, and cadmium salts had no significant effects. Other experiments with a heavy Venezuelan oil showed that, contrary to earlier suggestions, the use of a ketal did not decrease fuel formation.

Effects of solvent molecular toxicity and microenvironment composition on the Δ1 dehydrogenataon activity of Arthrobacter simplex cells

Solvent selection tests were carried out for the Delta(1) dehydrogenation of 6-alpha-methylhydrocortisone-21-acetate by Arthrobacter simplex cells in the presence of organic solvents. Solubility limits were determined for substrate and product in dry and water-saturated solvents and solvent mixtures. Molecular toxicity levels were estimated by measuring the dehydrogenation activity decay of freely suspended cells incubated in solvent-saturated aqueous media. Chloroform and n-decan-1-ol were the best choice of solvent, for both solubility and catalytic stability. High concentrations of water-soluble additives, such as monosodium glutamate, were found to greatly improve the retention of activity in chloroform-saturated media.

Hydration and Hardening of Apatitic Cement

Abstract Hydroxyapatite (HAp) with the general formula Ca10 z(HPO4)z (PO4) 6-z (OH) a-z · nH2O has become of particular interest as a bio-restorative material having good compatibility with living hard tissues. In this work, hydration and hardening properties of water-setting apatitic cements were presented. Ca3(PO4)2 with the formd α (α-TCP) itself was an apatitic cement which could hydrate and harden alone, and formed HAp or Ca8H2 (PO4) 6 · 5H2O (OCP). Other apatitic cements were prepared by mixing at least two compounds selected from Ca HPO4 · 2H2O (DCPD), α-TCP, Ca4(PO4)aO (TeCP) and CaCO3. The hydraulic reaction of α-TCP was accelerated by using water-soluble additives such as NaCl, NH4Cl, NH4 -citrate, etc. Another way for the acceleration was the addition of DCPD. The combination α-TCP/DCPD was developed with the expectation of the reaction α-TCP + DCPD + H2O → 1/2 OCP. Hydraulic reactions of combinations TeCP/DCPD (Brown and Chow, 1983) and DCPD/CaCO3 were also investigated. Various setting times ...

Release Kinetics of Tobramycin Sulfate from Polymethylmethacrylate Implants

AbstractThe effects of various formulation factors on the in vitro release characteristics of spherical polymethylmethacrylate implants were studied. Physical and mathematical models were proposed to describe observed in vitro release profiles. The in vitro release data could be described by a biexponential equation of the type: fraction of tobramycin remaining in the implant at time t = Ae−αt + Be−βt, where α and β represent the rate constants for the initial rapid and subsequent slow phases of release. The influence of drug loading, volume of dissolution medium, implant size, type of commercial cement and the incorporation of water soluble additives on the release profiles as well as the α and β rate constants is described

Disintegration of hard gelatin capsule formulations in the dog stomach — a radiological study

The final decision as to the suitable composition of an oral drug formulation should be made on the basis of in vivo studies. A radiological technique was developed for studying the in vivo disintegration of hard gelatin capsules in the stomach of the dog. Highly water-soluble additives such as sucrose and lactose caused rapid disintegration (10–15 min). Formulations containing semisolid material disintegrated in roughly 20 min. The mean disintegration time for capsules containing microcrystalline cellulose or dicalcium phosphate dihydrate was 37 min and 44 min, respectively. Capsules containing corn starch or carboxymethylcellulose sodium disintegrated very slowly and clearly adhered to the gastric mucosa. Very rapid disintegration (mean 9 min) was observed with capsules containing small coated pellets, which indicates that hard gelatin capsules may be a good dosage form for multiparticular modified-release formulations. The correlation between in vitro and in vivo data was unsatisfactory.

Studies of Interaction Phenomena in Aqueous-Based Film Coatings Containing Soluble Additives Using Thermal Analysis Techniques

Interaction phenomena, in aqueous-based hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA) film-coating formulations containing water-soluble additives (citric acid and urea) have been examined by thermal methods to assess glass transition, softening, melting, plasticization, and crystallinity. The methods used were differential scanning calorimetry (DSC) and thermomechanical analysis (TMA) in penetration and expansion modes. In addition to the established thermal transitions occurring in HPMC and PVA at relatively high temperatures, transitions were also observed between 26 and 43°C using TMA. These low temperature transitions, unlike those occurring at the higher temperatures, were low energy transitions and not influenced by the type and concentration of the additives incorporated. The results also showed that the plasticizing activities of citric acid and urea were as high as those of some currently used plasticizers. On a weight basis, urea was superior to citric acid as a plasticizer for either HPMC or PVA, but when their molar contents were considered, the position was reversed. Also, PVA crystallinity was depressed in the presence of the additives.