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Effects of oral chemical irritation on taste.

Oral irritation was induced by rinses with capsicum oleoresin and with piperine, constituents of red and black pepper, respectively. The perceived intensities of two concentrations of each of four tastants representing the four classical taste qualities were evaluated after rinsing with these irritants. Comparing taste intensity after rinses with capsicum and after control rinses with emulsifying agents or water, there were significant decrements in taste intensity of citric acid and quinine, and on one concentration of sucrose, but no effect on salt. The effects of piperine were more broad, with significant decrements in perceived intensity relative to emulsion controls for all substances.

Adult↗

Immunomodulatory effects of neem (Azadirachta indica) oil.

Immunomodulatory effects of neem oil were studied in mice. The animals were treated intraperitoneally (i.p.) with neem oil; control animals received the emulsifying agent with or without peanut oil. Peritoneal lavage, collected on subsequent days, showed a maximum number of leukocytic cells on day 3 following treatment with neem oil; peritoneal macrophages exhibited enhanced phagocytic activity and expression of MHC class-II antigens. Neem oil treatment also induced the production of gamma interferon. Spleen cells of neem oil-treated animals showed a significantly higher lymphocyte proliferative response to in vitro challenge with Con A or tetanus toxoid (TT) than that of the controls. Pre-treatment with neem oil, however, did not augment the anti-TT antibody response. The results of this study indicate that neem oil acts as a non-specific immunostimulant and that it selectively activates the cell-mediated immune (CMI) mechanisms to elicit an enhanced response to subsequent mitogenic or antigenic challenge.

Adjuvants, Immunologic↗

The effect of handcream on the antibacterial activity of chlorhexidine gluconate.

A series of handwashing experiments compared the residual effect on Escherichia coli of non-medicated soap, chlorhexidine detergent followed by an anionic handcream, chlorhexidine detergent followed by a non-ionic handcream and chlorhexidine detergent alone. Handcreams containing an anionic emulsifying agent reduced the antibacterial effect of chlorhexidine.

Chlorhexidine↗

Developmental toxicity of 1,1,1-trichloroethane in CD rats.

1,1,1-Trichloroethane (TCEN), a major industrial and household solvent, was evaluated for pre- and postnatal developmental effects in Sprague-Dawley rats. This study was designed to assess the repeatability of a report (S.C. Dapson, D.E. Hutcheon, and D. Lehr, Teratology 29, 25A, 1984) that indicated that 10 ppm TCEN in drinking water caused cardiac malformations in developing rats. In the present study, TCEN (97% pure) was administered in the drinking water at target concentrations of 3, 10, and 30 ppm, using 0.05% Tween 80 as an emulsifying agent. Two control groups, one receiving deionized/filtered water and the other receiving a vehicle control solution containing 0.05% Tween 80 and 0.9 ppm 1,4-dioxane, a stabilizing agent found in the bulk chemical, were also included. Male and female breeders (more than 30 per group) were exposed to the control solutions or test compound for 14 consecutive days prior to cohabitation and for up to 13 days during the cohabitation phase. Sperm-positive females (24-29 per group) continued to be exposed to these formulations during pregnancy and lactation to Postnatal Day (PND) 21. Parental animals exhibited a slight aversion to the 30-ppm drinking water during the premating exposure. No significant effect on reproductive competence of the parental animals or postnatal growth and development of the offspring to PND 21 was noted. A slight increase in mortality from implantation to PND 1, possibly due to high mortality in one litter, was observed in the 30-ppm dose group. There was no indication of an increase in the incidence of cardiac or other malformations in PND 21 pups. In summary, TCEN administered at 3, 10, and 30 ppm in the drinking water had no significant effect on the morphological development of CD rats.

Animals↗

Interactions of Solutol HS 15 and Cremophor EL with plasma lipoproteins.

Two emulsifying agents, Solutol HS15 and Cremophor EL, were compared with regard to their effects on human plasma lipoproteins in vitro and on mouse plasma lipoproteins in vitro and in vivo. Both agents promoted binding of a hydrophobic photosensitizing agent (C8KC) to a circulating plasma species of low bouyant density. Persistence of this material was greater with Cremophor than with Solutol. Experiments carried out with labeled Solutol indicated that the vehicle itself is a component of this new species. High concentrations of either vehicle ( > or = 0.06%) led to decreased electrophoretic mobility of human LDL and HDL in vitro. In the mouse, a different effect was observed, resulting in complex changes in electrophoretic mobility of plasma lipoproteins. The plasma half-life of C8KC in the circulation of the mouse was correlated with the persistence of an altered electrophoretic lipoprotein pattern. Since Solutol and C8KC showed similar half-lives, this result suggests that the plasma half-life of the sensitizer is correlated with the persistence of the vehicle. While Solutol and Cremophor were designed to be vehicles for drug formulation, they also influence persistence of some drugs in the circulation.

Animals↗

Microbial synthesis of poly(epsilon-lysine) and its various applications.

This review article deals with the microbial synthesis, physiochemical properties, and potential applications of poly-epsilon-lysine (epsilon-PL), which is a naturally occurring biomaterial that is water soluble, biodegradable, edible and non-toxic toward humans and the environment. The potential applications of epsilon-PL as food preservatives, emulsifying agent, dietary agent, biodegradable fibers, highly water absorbable hydrogels, drug carriers, anticancer agent enhancer, biochip coatings in the fields of food, medicine, agriculture and electronics are also discussed in this review.

Bacteria↗

Adsorption at the air-water interface and emulsification properties of grain legume protein derivatives from pea and broad bean.

Functional properties of native and modified (through induced autolysis) pea (Pisum sativum L.) and broad bean (Vicia faba L.) protein derivatives are studied. In specific, protein solubility and behavior at the air-water interface through surface pressure measurements are investigated. Furthermore the ability of the protein products to act as emulsifying agents and to stabilize emulsions is studied through oil droplet size distribution measurements and by the protein adsorbed at the oil-water interface. The data reveal that the ability of the proteins to act as surfactants and build up a rigid film around the oil droplets, mainly depends on their suitable molecular configuration and structure. Hydrolysis did not promote the functionality of the legume proteins. Broad bean exhibited better functionality than pea, before and after hydrolysis. Some comparisons were also made with lupin (Lupinus albus L.) protein isolate.

Adsorption↗

New surface-active polymers for ophthalmic formulations: evaluation of ocular tolerance.

Two n-octenylsuccinate starch (AS) types of unknown molecular weights were assessed for ocular tolerance. Irritation potential of different solutions (containing 2 and 15% (w/w) AS) and AS stabilized emulsions (containing 15% (w/w) AS) was evaluated in vivo in rabbit eyes, using a confocal laser scanning microscope, and in vitro on treated excised pig corneas by light microscopy of histological cross sections. Both AS types were previously characterized by viscosity, osmolality and surface tension measurements. All tested solutions and emulsions showed good eye tolerance regardless of concentration and emulsifying properties suggesting AS to be a good alternative to commonly used solubilizing or emulsifying agents in ophthalmic formulations.

Animals↗

Comparative scale-up of three methods for producing ibuprofen-loaded nanoparticles.

The lack of information related to the scaling-up of technologies used for preparing polymeric nanoparticles (NP) might hinder the introduction of these colloidal carriers into the pharmaceutical market. In the present study, the scale-up of ibuprofen-loaded NP produced by three manufacturing processes--salting-out, emulsification-diffusion and nanoprecipitation--was assessed at pilot-scale by increasing 20-fold the laboratory-batch volume from 60 ml to 1.5l. Eudragit L100-55 and poly(vinyl alcohol) (PVAL) were used as polymer and emulsifying agent, respectively. The influence of the hydrodynamic conditions on the NP characteristics such as mean size, drug content, residual PVAL and morphology was also investigated. At pilot-scale, stirring rates of 790-2000 rpm lead to NP mean sizes ranging from 557 to 174 nm for salting-out and from 562 to 230 nm for emulsification-diffusion. An increase in the stirring rate enhances the droplet break-up phenomenon which leads to the formation of finer emulsion droplets and thus smaller NP. Moreover, the influence of the stirring rate on the mean size of NP can be predicted using a model based on a simple power law. The continuous method used for nanoprecipitation scale-up allows production of NP in a reproducible way over a relatively short time. Finally, for the three methods, NP characteristics were reproduced well at both scales. However, the scale-up process induced a slight reduction in the size and drug loading of NP.

Chemical Precipitation↗

Clinical application of 11-deoxycortisol in visualizing prolapsed vitreous body after posterior capsule rupture in cataract surgery.

PURPOSE: To evaluate the clinical usefulness of 11-deoxycortisol, a precursor of cortisol in steroid metabolism, in visualizing the vitreous body in the anterior chamber after posterior capsule rupture during cataract surgery. SETTING: Department of Ophthalmology, Tsukuba University Hospital, Ibaraki, Japan. METHODS: Eight eyes had anterior vitrectomy during cataract surgery using this new technique. A suspension of 11-deoxycortisol was prepared by dilution in balanced salt solution without preservatives or emulsifying agents. After a posterior capsule rupture, the suspension was injected into the anterior chamber. The visual and anatomical outcomes of surgery were evaluated during a follow-up of 7 to 9 months. RESULTS: After the 11-deoxycortisol injection, the vitreous body that had prolapsed through the torn posterior capsule, with white particles entrapped on its surface, became clearly visible. Complete removal of the prolapsed vitreous body was achieved easily and safely using an anterior vitrectomy system. No postoperative complications related to the use of 11-deoxycortisol were observed. CONCLUSION: Injection of 11-deoxycortisol helped visualize the vitreous body in the anterior chamber after posterior capsule rupture. The technique minimized intraoperative and postoperative complications related to posterior capsule rupture and vitreous loss during cataract surgery [corrected]

Aged↗

Quantitation of poloxamers in pharmaceutical formulations using size exclusion chromatography and colorimetric methods.

Poloxamers have been used as functional excipients in pharmaceutical products. They function as surfactants, emulsifying agents, solubilizing agents, dispersing agents, and in vivo absorbance enhancer. Despite their wide range of applications, limited analytical techniques have been reported in literature for characterizing poloxamers and few are targeted to quantify poloxamer contents in formulations with desired sensitivity and accuracy. In this paper, two distinct analytical methods for quantifying low levels of poloxamers in pharmaceutical formulations have been developed and optimized: a colorimetric method and a size exclusion chromatography method. The colorimetric method is based on the formation of a colored complex between poloxamers and cobalt(II) thiocyanate in aqueous medium, which has a maximum UV absorbance at 624 nm. The feasibility of this method is product specific. In this report, adequate specificity and sensitivity was demonstrated for only one of the several products tested. The size exclusion chromatography (SEC) method utilizes size exclusion columns with THF as mobile phase and refractive index detection. The SEC method provides a limit of quantitation (LOQ) of 0.005 mg/mL (0.0005%, w/w) and at least three orders of magnitudes of linear range. We applied the SEC method to pharmaceutical products containing 0.3-10% poloxamer 188 or poloxamer 407, such as Avapro, Neurontin, Sudafed and other developmental formulations. The results obtained with the SEC method agreed very well with literature and theoretical values with 97-102% recovery. The SEC method was proven to be widely applicable, accurate, precise and simple to use.

Amines↗

Fluorocarbons: a potential treatment of cerebral air embolism in open-heart surgery.

This study was designed to assess whether an oxygenated fluorocarbon solution could reduce ischemic brain damage related to arterial air embolism. Air embolism was produced by injecting air bubbles into the carotid artery of barbiturate-anesthetized rats breathing 100% oxygen. Results were assessed on electrocorticogram. In an additional set of experiments, mass spectrometry was used to provide continuous monitoring of intracerebral tissue oxygen (PO2) and carbon dioxide (PCO2) tensions and intermittent measurement of cerebral blood flow (CBF). Fluorocarbon or saline solution (containing the emulsifying agent of fluorocarbons) was given intravenously after the initial air embolism (0.2 ml), and injections of air (0.1 ml) were repeated thereafter every five minutes. The maximal amount of air required to achieve complete and irreversible flattening of the electrocorticogram was 1.60 +/- 0.06 ml (mean +/- standard error of the mean) in the saline-treated rats and 5.20 +/- 0.44 ml in the fluorocarbon-treated group (p less than 10(-7)). In the second experiment, air embolism caused CBF to rise in both groups, the average percent of increase being higher in treated (41.6%) than in control animals (38.3%) (p less than 0.02). However, in the control group, the increase in CBF did not prevent intracerebral tissue PO2 from decreasing by 7.4 +/- 7.0% over the same period; conversely, in the fluorocarbon group, PO2 levels fell by only 2.5 +/- 3.7% (p less than 0.001 versus controls), but this time-averaged percentage was calculated over a longer period of cumulative ischemia because of the greater number of air emboli tolerated by treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Red blood cell substitutes and artificial blood.

Artificial substitutes for specific functional portions of blood are being developed. Perfluorocarbons have received the most publicity in recent years, and one, Fluosol-DA, is undergoing clinical trials in the United States. The perfluorocarbon emulsions physically dissolve oxygen, which distinguishes them from the chemical binding that occurs in hemoglobin. Fluosol-DA has been shown to transport oxygen in amounts that are probably clinically useful if the patient inspires an atmosphere with increased oxygen. A large clinical trial from Japan suggests that Fluosol-DA is safe to transfuse, although recent work suggests that Fluosol-DA may produce significant pulmonary reactions that can be prevented by steroid administration. These reactions are probably caused by complement activation by an emulsifying agent in Fluosol-DA. Recent applications of Fluosol-DA include use in a resuscitative fluid, use in occlusive vascular disease, an special applications, such as treatment of carbon monoxide poisoning, which take advantage of the solubility properties of perfluorocarbons.

Anemia, Sickle Cell↗

Apolipoprotein B and low-density lipoprotein structure: implications for biosynthesis of triglyceride-rich lipoproteins.

ApoB100 is a very large glycoprotein essential for triglyceride transport in vertebrates. It plays functional roles in lipoprotein biosynthesis in liver and intestine, and is the ligand recognized by the LDL receptor during receptor-mediated endocytosis. ApoB100 is encoded by a single gene on chromosome 2, and the message undergoes a unique processing event to form apoB48 message in the human intestine, and, in some species, in liver as well. The primary sequence is relatively unique and appears unrelated to the sequences of other serum apolipoproteins, except for some possible homology with the receptor recognition sequence of apolipoprotein E. From its sequence, structure prediction shows the presence of both sheet and helix scattered along its length, but no transmembrane domains apart from the signal sequence. The multiple carbohydrate attachment sites have been identified, as well as the locations of most of its disulfides. ApoB is the single protein found on LDL. These lipoproteins are emulsion particles, containing a core of nonpolar cholesteryl ester and triglyceride oil, surrounded by an emulsifying agent, a monolayer of phospholipid, cholesterol, and a single molecule of apoB100. An emulsion particle model is developed to predict accurately the physical and compositional properties of an LDL of any given size. A variety of techniques have been employed to map apoB100 on the surface of the LDL, and all yield a model in which apoB surrounds the LDL like a belt. Moreover, it is concluded that apoB100 folds into a long, flexible structure with a cross-section of about 20 x 54 A2 and a length of about 585 A. This structure is embedded in the surface coat of the LDL and makes contact with the core. During lipoprotein biosynthesis in tissue culture, truncated fragments of apoB100 are secreted on lipoproteins. Here, it was found that the lipoprotein core circumference was directly proportional to the apoB fragment size. A cotranslational model has been porposed for the lipoprotein assembly, which includes these structural features, and it is concluded that in permanent hepatocyte cell lines, apoB size determines lipoprotein core circumference.

Amino Acid Sequence↗

Adrenaline-cocaine gel topical anesthetic for dermal laceration repair in children.

STUDY OBJECTIVE: To evaluate the anesthetic efficacy of a gel form of adrenaline-cocaine topical medication for minor dermal laceration repair. DESIGN: Unblinded, prospective. SETTING: An urban pediatric emergency department. TYPE OF PARTICIPANTS: Thirty-five children aged 20 months to 18 years with lacerations of the face, outer lip, and scalp. INTERVENTIONS: All received adrenaline-cocaine gel made by mixing 1.5 mL of conventional adrenaline-cocaine liquid (adrenaline, 1:2,000; cocaine, 11.8%) with 0.15 g of methylcellulose powder (an inert emulsifying agent). MEASUREMENTS AND MAIN RESULTS: Lacerations were located on the face or outer lip in 25 patients and on the scalp in ten patients. Larger lacerations (length of more than 5 cm and/or depth of more than 5 mm) occurred in nine patients. The average dose of adrenaline-cocaine gel applied per laceration was 0.35 mL (containing 40 mg cocaine). One hundred ninety-five sutures were placed (175 cutaneous, 20 subcutaneous); 192 (98.5%) were placed without eliciting any pain. There were no observed adverse reactions with adrenaline-cocaine gel administration or reported complications of wound healing in any patient. CONCLUSION: Adrenaline-cocaine gel preparation provides excellent anesthetic efficacy for minor dermal lacerations in children. Compared with conventional adrenaline-cocaine liquid, adrenaline-cocaine gel may be advantageous in reducing the total cocaine requirement and may diminish the risk for adverse reactions that can result from runoff of liquid medication onto mucosal or ocular surfaces.

Administration, Topical↗

Spray-dried redispersible oil-in-water emulsion to improve oral bioavailability of poorly soluble drugs.

A physically stabilized dry emulsion dosage form reforming the original emulsion after rehydration was developed by spray-drying a liquid oil-in-water emulsion containing maltodextrin as carrier and sodium caseinate as emulsifying agent. Several oil:water as well as maltodextrin:water ratios were tested, the homogenization and spray-drying processes and the reconstitution properties were investigated and an optimum formulation was selected for poorly soluble drug incorporation, having an identical oil:water and carrier:water ratio of 10% (w/w) and a load of solid material of 20% (w/w). Lipophilic 5-phenyl-1,2-dithiole-3-thione (5-PDTT) was selected as a model drug. 5-PDTT release from the solid state emulsion was studied using an in vitro two-phase stirred model and the relative bioavailability of 5-PDTT in the dry emulsion was obtained in the rabbit after oral administration of the reconstituted emulsion, compared to a 5-PDTT-sulfobutyl ether 7 beta-cyclodextrin complex in solution. Incorporation of 5-PDTT in the oil phase neither affects the surface morphology of the powder nor the reconstitution, the droplet size or the drug releasing properties and, furthermore, allows a 3-fold improvement of 5-PDTT relative bioavailability in rabbit after oral administration. These results indicate that dry emulsions may be considered as relevant dosage forms to improve bioavailability of poorly absorbable lipophilic drugs.

Administration, Oral↗

Bioavailability of diazepam from aqueous-organic solution, submicron emulsion and solid lipid nanoparticles after rectal administration in rabbits.

The bioavailability of diazepam in rabbits after rectal administration of three formulations: organic-aqueous Relsed rectal solution (containing ethanol, benzyl alcohol and propylene glycol), submicron emulsion and solid lipid nanoparticles (SLN), was studied. Submicron emulsion contained MCT oil (20% w/w), egg lecithin and poloxamer; SLN were prepared with cetyl palmitate 10% w/v and non-ionic emulsifying agent, Plantacare. All formulations contained 4 mg/ml of diazepam and the dose administrated to rabbits was 2 mg/kg. In both submicron preparations nearly the same mean size of the dispersed particles (201-206 nm) and the fraction of the free drug in aqueous phase (0.9-1.5%) was determined. Besides very moderate prolongation of drug release, the submicron emulsion as a vehicle did not alter pharmacokinetics of diazepam when compared with the solution: the mean C(max) was 48.9+/-24.0 and 49.5+/-17.0 ng/ml, and area under the curve was 134.0+/-42.3 and 186.8+/-59.8 ng h/ml, for solution and emulsion, respectively. The low relative bioavailability, 47% compared to the solution, was observed after administration of SLN. Transmission electron microscopy pictures revealed that some of diazepam is present on the surface of the SLN and this fraction was immediately absorbed, while the diffusion of the drug in the solid core was not efficient enough to allow a complete release. It may be concluded that submicron emulsion may be a good choice of an ethanol-free drug formulation, but lipid matrix, which is solid at body temperature, is not advantageous system for diazepam rectal delivery, even if delivered as a submicron dispersion.

Administration, Rectal↗