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Lack of efficacy of polysorbate 60 in the treatment of male pattern baldness.

Anecdotal reports have indicated that the nonionic detergent polysorbate 60 may be of some value in male pattern baldness. In this double-blind placebo-controlled trial, a photographic and objective scalp measurement system was developed to assess new hair growth. No significant difference was detected between subjects treated for 16 weeks with polysorbate 60 and control subjects treated with glycerin, indicating that polysorbate 60 is ineffective. Of the 141 subjects who completed the trial, 25% perceived that they grew new hair, 67% said they did not, and 8% were uncertain. Subject-reported new hair growth did not correlate with measurements, indicating that the placebo effect may be a major factor in reports of baldness "cures".

Adult

Polysorbate 80 and E-Ferol toxicity.

The relatively recent introduction and use of an intravenous form of a vitamin E preparation (E-Ferol) has been associated with the development of an unusual syndrome and fatalities among low birth weight (less than 1,500 g), premature infants in neonatal intensive care units. We have observed an inhibitory effect by this vitamin E preparation on the in vitro response of human lymphocytes to phytohemagglutinin (PHA). E-Ferol suppressed the expected response to low doses of PHA. However, this suppression was not due to the alpha-tocopherol acetate (vitamin E) component, because alpha-tocopherol acetate by itself was not inhibitory; in fact, it often enhanced the PHA response. Because a mixture of polysorbate 80 and polysorbate 20 is used as a carrier in E-Ferol, these components were also tested and were found to be responsible for the suppression, especially the polysorbate 80. Concurrent with this suppression of PHA-induced mitogenesis was a decrease in the percentage of T11 lymphocytes.

Humans

Effect of polysorbate 60 on interphase transport of cholesterol.

Interphase cholesterol transport was investigated at 24 +/- 1 degrees in a stirred diffusion cell and in various oil-in-water emulsions. Cholesterol uptake by vegetable oil from a cholesterol-surfactant-rich aqueous phase was extremely slow in the stirred cell; no measurable transport had occurred after 500 hr. Cholesterol transport in oil-in-water emulsions following dilution with a cholesterol-surfactant-rich aqueous phase was much faster due to the greatly increased interfacial area available for mass transfer. Equilibration half-lives, t(50), varied from 2.02 to 28.1 hr. Variations in the t(50) were due to: (a) differences in the mean oil droplet diameter among various emulsions, and (b) differences in cholesterol-polysorbate 60 micelle sizes among various dilution media. When polysorbate 60 was omitted from the dilution medium, transport occurred in a two-stage process. In the first stage, transport was extremely rapid, with the t(50) less than 30 sec; in the second stage, transport was comparable to previous emulsion rates, with the t(50) varying from 7.9 to 8.1 hr. The significance of this two-stage transport to mechanisms of interphase cholesterol transport is briefly discussed.

Cholesterol

Effect of sorbitol on interaction of phenolic preservatives with polysorbate 80.

The effect of sorbital on the binding of several commonly used phenolic preservatives (i.e., p-hydroxybenzoic acid, methylparaben, ethylparaben, and propylparaben) with the nonionic surfactant polysorbate 80 was investigated using an equilibrium dialysis technique. The binding data were expressed in the form of Scatchard plots utilizing a modified form of the Scatchard equation. The data analysis indicated that all four phenolic preservatives were bound to two distinct loci within the polysorbate micelle; one exhibited a high affinity and a low capacity for the preservative molecules, while the other appeared to have a near-zero affinity but an almost infinite binding capacity. The high affinity site was assumed to be located near the junction of the hydrocarbon core with the polyoxyethylene region of the micelle. The interaction of the preservatives with the second class of sites apparently involved a non-specific and nonsaturable partitioning of the preservative molecules into the polyoxyethylene region of the micelle. Sorbitol was ineffective in displacing significant amounts of bound preservative from either binding site, presumably because it was too polar to partition into the micelle sufficiently to displace bound preservative.

Chemical Phenomena

Autoxidation of polysorbates.

Aqueous solutions of polysorbate 20 undergo autoxidation on storage, with the peroxide number increasing and subsequently decreasing again, the acidity increasing continuously, the pH and surface tension falling and tending to level off, and the cloud point dropping sharply until turbidity begins at room temperature. The changes are accelerated by light, elevation of temperature, and a copper sulfate catalyst. At the same time, hydrolysis occurs, liberating lauric acid. Analysis of the alterations in these properties leads to the conclusion that hydrolysis has the major influence near room temperature and that oxyethylene undergoes chain shortening at temperatures above 40 degrees. However, evidence of degradation is detectable even in previously unopened commercial samples of polysorbates 20, 40, and 60, warranting attention to the stability of and standards for these surfactants as compared with the solid alkyl ether type of nonionic surfactant.

Chemical Phenomena

Effect of polyols on interaction of paraben preservatives with polysorbate 80.

A quantitative study of the interaction of the methyl, ethyl, propyl, and butyl esters of p-hydroxybenzoic acid with polysorbate 80 in the presence and absence of two polyols (propylene glycol and glycerol), which were potential competitors, was performed. The results indicate that neither competitor displaced significant amounts of the parabens from their binding sites on polysorbate 80. The previously observed synergistic antimicrobial effects of these polyols appear to be due to a mechanism other than the displacement of the parabens from their micellar binding sites.

Alcohols

Ionophoric properties of polysorbate 80.

Polysorbate 80, a surfactant often assumed to be inert, was found to bind a number of biochemically important ions (K+, Na+, NH4+, Ca2+) and transport them through a model membrane (CH2Cl2). The rates and fluxes of potassium ions were found to depend on the initial concentration of potassium ion, the polysorbate 80 concentration, the temperature, and the stirring rate. The thermodynamic constants for the process were determined and its mechanism is discussed.

Chemical Phenomena

The effect of sodium lauryl sulphate, cetrimide and polysorbate 20 surfactants on complex coacervate volume and droplet size.

The effects of sodium lauryl sulphate (SLS), cetrimide and polysorbate 20 surfactants at concentrations below, at and above their critical micelle concentration (CMC) on the complex coacervation of varying concentrations of gelatin and acacia have been described. The overall effect of increasing concentration of SLS was to reduce the weight of coacervate formed. The addition of increasing concentrations of cetrimide produced an increase in the weight of coacervate. The two lowest concentrations of polysorbate 20 produced an increase in coacervate weight while the highest concentration, above the CMC, reduced the coacervate weight. These effects have been explained in terms of shielding of electrostatic attractions between gelatin and acacia polyions by adsorption of ionic and non-ionic surfactant molecules onto the polyions. The addition of surfactants influenced the size distribution of the coacervate droplets that were produced. It is believed that the reduction in interfacial tension by the aggregation of surfactant molecules at the coacervate-equilibrium liquid interface permitted the formation of smaller coacervate droplets.

Capsules

Quantitative determination of polysorbate to in non-standard salad dressings.

Six samples of non-standard salad dressing, containing 0.10 to 0.60% polysorbate 60, were submitted to 6 collaborators. The salad dressing is extracted and the extract is saponified and acidified, and the acids are removed. The aqueous, polyol solution is desalted and the polyoxyethylated polyols are precipitated as a highly insoluble heteropoly acid complex. The polysorbate 60 content is calculated from the weight of the precipitate, using a gravimetric factor. Average recoveries from the collaboration samples ranged from 105 to 130%, with standard deviations from 0.016 to 0.047. The method has been adopted as official first action.

Food Additives

Effect of polysorbate 85 on human skin.

Ten percent polysorbate 85, a nonionic surfactant, was applied on the upper arm of 15 healthy individuals under occlusive dressing daily for 4 days. The other arm was similarly treated with the ointment base (white petrolatum USP) to provide the control area. At the end of treatment, macroscopic observations indicated minor erythema in 11 cases and no visible changes were noted on the surfactant-treated areas of 4 persons or any of the control areas. No definite histologic changes were observed by microscopic evaluations. The results of biochemical assays, however, were more definitive. The content of the epidermal phospholipids was elevated within a range of 5 to 65 percent as a result of the treatment with polysorbate 85 preparation. Radioactive tracer studies indicated higher rates of 32P incorporation into epidermal phospholipids, TCA-soluble, DNA and RNA fractions of the surfactant-treated skin. Results resemble those that were documented in earlier studies with rabbit skin.

Adult

[The effect of polysorb on the course of the wound process].

The peculiarities of a contact of the sorbent particles of a polysorb for medical purposes with the somatic cells have been studied. The destructive action of the preparation its capability to block the functionally active sites of a cellular membrane were revealed. The recommendations on clinical use of a polysorb have been developed.

B-Lymphocytes

Interaction of substituted benzoic acids with polysorbate 20 micelles.

Equilibrium solubilities of a series of substituted benzoic acids in different concentrations of polysorbate 20 at controlled pH were measured. The maintenance of pH was achieved using a pH-stat assembly. A linear relationship was found between the amount of benzoic acid solubilized and surfactant concentration. As solubilizate polarity increased, the amount solubilized also increased. Solubility data were analyzed, and the interaction between solubilizate molecules and micelles was calculated in terms of partition coefficients of ionized and unionized molecules between aqueous and micellar phases. A linear relationship between pi values (log partition coefficients) of functional groups and aqueous-micellar partition coefficient was found.

Benzoates

Influence of polysorbate 80 (Tween 80) and etoposide (VP-16-213) on the pharmacokinetics and urinary excretion of adriamycin and its metabolites in cancer patients.

Polysorbate 80 (Tween 80) is present in the IV pharmaceutical preparation of VP-16-213 marketed as VePesid (Bristol-Myers) (etoposide 100 mg, benzylalcohol 150 mg, polyethylene glycol 300 3250 mg, citric acid 10 mg, Tween 80 400 mg and absolute alcohol to 5 ml per 100 mg ampule of VP16), to increase its miscibility with blood. We have examined the effects of 400 mg/m2 Tween 80 IV and 100 mg/m2 VP16 on the pharmacokinetics of Adriamycin (ADR, 30 or 40 mg/m2). ADR and metabolite concentrations were measured by HPLC. ADR plasma profiles were best fitted to a bi-exponential decay and a two-compartment open model. Tween 80 did not alter the values of the two ADR half-lives, nor did it affect metabolite kinetics of their urinary excretion. However, in a similar manner and consistently in all patients, both Tween 80 and VP16 increased the volume of distribution of the central compartment for ADR up to 3-fold, decreased the AUC of ADR up to 2-fold and increased its clearance by exactly the same amount. These effects were due to reduced plasma ADR concentrations during the early phase of its kinetics. Urinary excretion of ADR was also increased. In conclusion, VP16 is likely to affect the kinetics of drugs administered with it: early plasma concentrations will fall due to a general physiological effect of Tween 80 on the apparent volume of circulation.

Adult

Determination of polysorbate in ascites fluid from a premature infant.

A method is described for the determination of poly(oxy-1,2-ethanediyl)oligomers in body fluids using ammonium cobaltothiocyanate complexation in conjunction with high pressure liquid chromatography and visible spectrophotometry. Analysis of peritoneal fluid from a baby given E-ferol, a vitamin E supplement, revealed levels as high as 100 micrograms/mL polysorbate.

Ascitic Fluid

Cmc of mixtures of chlorpromazine hydrochloride and polysorbate 80 determined by pH measurements.

The cmc of mixtures of chlorpromazine hydrochloride and polysorbate 80 was determined by pH titration. The values thus obtained coincided with those determined by the surface tension method. The mixtures studied could be divided into two groups according to the shape of their pH concentration curves. For mixtures containing less than 0.8 mole fraction chlorpromazine, the curves suggest that some interaction occurs in the premicellar concentration range. For mixtures containing more than 0.8 mole fraction chlorpromazine, the curves suggest that the micellar process occurs in more than one step.

Chemistry, Pharmaceutical

Enhanced rectal absorption of itazigrel formulated with polysorbate 80 micelle vehicle in rat: role of co-administered esterase.

We investigated the effect of esterase on rectal absorption in the rat of itazigrel using polysorbate 80 (PS-80) micelle as a vehicle to overcome the poor aqueous solubility of itazigrel. The itazigrel formulation prepared with PS-80 increased the absorption compared with a 0.25% carmellose sodium suspension, probably by supplying the itazigrel solute to keep a high concentration at the epithelial surface. When esterase was co-administered with the formulations containing PS-80, the absorption of itazigrel from rat rectum was accelerated further, by rapid release of itazigrel from the micelle vehicle after enzymatic degradation of the PS-80 micelle.

Absorption

Polysorbate 80 and low-osmolality water-soluble contrast medium enema in diagnosis and treatment of faecal obstruction in malignant phaeochromocytoma. Report of a case.

Stercoral obstruction in a young woman with disseminated phaeochromocytoma was diagnosed and treated successfully using an enema of isosmolar iohexol (Omnipaque) and 1% polysorbate 80 (Tween 80) without complication. Surgical intervention was thus avoided. A low osmolality water-soluble contrast medium (iohexol 150 mg I/ml) with a wetting agent (1% Tween 80) was used because a barium suspension would have inspissated, exacerbating the constipation and a hyperosmolar contrast medium might have precipitated a hypertensive crisis and destabilized her critical salt and water balance.

Adrenal Gland Neoplasms