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PubMed2000

Effect of polyoxyl 35 castor oil and Polysorbate 80 on the intestinal absorption of digoxin in vitro.

Surfactants are classically used to improve the solubilization of lipophilic drugs such as digoxin. Polysorbate 80 and Cremophor EL (polyoxyl 35 castor oil) are such surfactants but they may also modulate the action of P-glycoprotein, an energy-dependent "counter-transport" system implicated in the phenomenon of multidrug resistance in cancer cells. P-glycoprotein is also present in the intestine on the apical membrane of mature enterocytes and can potentially reduce the absorption of a wide range of drugs. In this study, using the improved everted gut sac method, the effects of Polysorbate 80, Cremophor EL and cyclosporin on the absorption of digoxin were studied. An increase in the uptake of digoxin in the presence of these three products could be shown with our in vitro model. Cremophor EL and Polysorbate 80 had no toxic effects at the concentrations used. These results suggest that surfactants such as Cremophor EL and Polysorbate 80 should not only support solubilization but can also modulate the P-glycoprotein system to improve the bioavailability of poorly absorbed drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Effect of polysorbates on atenolol release from film-coated tablets.

The effects of different concentrations of various polysorbates on the release rate of atenolol from film-coated tablets were evaluated. The release profile of atenolol showed that increasing the concentration of polysorbate resulted in an increase in the release rate of atenolol. The type of polysorbate had less effect on the release rate of atenolol. This study revealed that the release kinetic of atenolol from these film-coated tablets was a function of polysorbate concentration. Correlation coefficients of kinetic models could not solely determine the suitability of the models; the sum of the least square of differences also should be calculated when different kinetic models have similar correlation coefficients.

Atenolol↗

PubMed2001

Increased vigabatrin entry into the brain by polysorbate 80 and sodium caprate.

The effects of a non-ionic surfactant, polysorbate 80, and the sodium salt of the saturated fatty acid, sodium caprate (C10), as potential brain absorption enhancers for vigabatrin were studied. Vigabatrin is an enzyme-activated irreversible inhibitor of gamma-aminobutyric acid (GABA) transaminase that increases brain and cerebrospinal GABA concentrations in animals and man. Before intravenous administration, a range of concentrations of the surfactants were tested using erythrocyte lysis or the red blood cell lysis test to establish the non-toxic concentration range. Vigabatrin was dissolved in 0.1% polysorbate 80 and 0.1% sodium caprate and administered intravenously in doses of 4 mL kg(-1) to male Wistar rats (230-250 g; n = 3). Rats were killed 2 h after drug and surfactant administration and the brains were immediately removed and homogenized in 0.4 M perchloric acid. Selected ion monitoring electrospray mass spectrometry was used to determine the concentration of vigabatrin and GABA directly from the perchloric acid extract of the rat brain. This method was developed to increase the speed and efficiency of the analysis by removing the need for complex extraction and derivatization procedures while retaining the specificity of the mass spectrometer as a detector. The stability of both vigabatrin and GABA in perchloric acid was established by monitoring their pseudo molecular ions in standard solutions at timed intervals over 24 h. Although the detection level for vigabatrin and GABA was at least 50 pg, only GABA was detected in rat brain. Vigabatrin caused a small increase in whole brain GABA. However, GABA levels were higher in the samples with vigabatrin + enhancer than in the samples where vigabatrin alone was administered. One-way analysis of variance indicated a significant effect of the surfactants on GABA levels (F (5,17) = 11.86, P < 0.01) and vigabatrin absorption was presumed. The rectal temperature of the rats is lowered by the presence of vigabatrin in the brain. Vigabatrin alone decreased rectal temperature by 6%. When given with either polysorbate 80 or sodium caprate, the extent of temperature lowering was significantly greater (P < 0.001). There was no significant difference after 2 h between polysorbate 80 + vigabatrin, and sodium caprate + vigabatrin.

Animals↗

PubMed1987

Analysis of polysorbate and its polyoxyethylated metabolite.

Polysorbates are used as emulsifiers in a number of pharmaceuticals and have been implicated as the possible toxic agent in the neonatal vitamin supplement, E-Ferol. In the investigation of the toxicity of this compound, it was necessary to find a method to separate and quantitate polysorbate and its polyoxyethylated metabolite from biological fluids. A high-performance liquid chromatography method was developed which combines the use of a 500 A mu Styragel size exclusion column with an ammonium cobaltothiocyanate complexation column and detection at 620 or 320 nm. The detection limit is approximately 5 micrograms. The method was used to demonstrate that polysorbate was metabolized in vitro by hepatocytes and that the urinary metabolite in humans is comparable to that produced by the rat.

Animals↗

PubMed2006

Influence of particle size on transport of methotrexate across blood brain barrier by polysorbate 80-coated polybutylcyanoacrylate nanoparticles.

Transports of methotrexate-loaded polybutylcyanoacrylate nanoparticles with different sizes across blood brain barrier were investigated in this experiment. The drug-loaded nanoparticles were prepared by emulsion polymerization method. After coating with polysorbate 80, nanoparticles with the size 70, 170, 220, 345 nm were, respectively, i.v. injected into rats at the dose of 3.2 mg/kg. Uncoated nanoparticles and methotrexate solution were also i.v. injected at the same dosage as controls. 0.5, 1, 1.5, 2, 3, 4 h after injection, cerebrospinal fluids and brain tissues were collected for tests. Drug level in all biological samples was determined by HPLC. It was found out that nanoparticles overcoated by polysorbate 80 could significantly improve the drug level in both brain tissues and cerebrospinal fluids compared with uncoated ones and simple solution. Seventy-nanometer nanoparticles could deliver more drugs into brain while no significant difference was observed among the other three size ranges. In conclusion, polysorbate 80-coated polybutylcyanoacrylate nanoparticles could be used to overcome blood brain barrier especially those whose diameter was below 100 nm.

Animals↗

PubMed2006

Polysorbate 80 UV/vis spectral and chromatographic characteristics--defining boundary conditions for use of the surfactant in dissolution analysis.

Polysorbate 80 is used in the pharmaceutical industry as an additive to enhance the solubility of non-polar compounds in formulation design and during dissolution analysis. In this paper we present the spectroscopic and chromatographic characteristics for a series of commercially available sources of this non-ionic surfactant. The large UV/vis absorbance and broad chromatographic elution of Polysorbate 80 often makes it difficult to accurately quantitate pharmaceutically active compounds in solutions where the surfactant is present. Boundary conditions have been established where analytical interferences can be avoided in spectrophotometric analysis by choice of analysis wavelength and solution concentrations. Chromatographic method development is also presented enabling the removal of Polysorbate interference in instances where spectroscopic interference is too great.

Chromatography, High Pressure Liquid↗

PubMed2003

Clinical pharmacokinetics of unbound docetaxel: role of polysorbate 80 and serum proteins.

OBJECTIVE: Our objectives were to study the extent of docetaxel binding to plasma in the presence and absence of its excipient, polysorbate 80 (Tween 80; Imperial Chemical Industries PLC, London, United Kingdom), in vitro and to evaluate the pharmacokinetics of unbound docetaxel in vivo. METHODS: Equilibrium dialysis was used for determination of the fraction unbound (f(u)) docetaxel and was applied to study the pharmacokinetic behavior of unbound docetaxel in 23 patients with cancer receiving an intravenous infusion of the drug formulated in polysorbate 80 (Taxotere; Aventis Pharma SA, Vitry-sur-Seine Cedex, France). RESULTS: Polysorbate 80, added at clinically relevant concentrations (up to 1.0 microL/mL), increased f(u) in vitro by 13% (7.84% +/- 0.0752% versus 6.95% +/- 0.0678%, P <.00001). Similarly, f(u) calculated on the basis of the observed area under the plasma concentration-time curve (AUC) values [f(u)(AUC)] in vivo was 12% higher than f(u) in pretreatment samples [f(u)(pre)] (6.00% +/- 1.03% versus 5.49% +/- 1.01%, P =.038). Of various serum proteins evaluated, only alpha(1)-acid glycoprotein was significantly related to f(u) (P <.0018), with higher f(u) in the presence of lower protein levels. Total docetaxel clearance was related to alpha(1)-acid glycoprotein (R(2) = 0.13, P =.058), f(u)(pre) (R(2) = 0.15, P =.039), and f(u)(AUC) (R(2) = 0.29, P =.0048). CONCLUSION: This study demonstrates that the plasma binding of docetaxel is influenced by both alpha(1)-acid glycoprotein and its formulation vehicle. Further investigation is required to resolve the potential clinical significance of these observations.

Adult↗

PubMed2002

Toxicological studies of doxorubicin bound to polysorbate 80-coated poly(butyl cyanoacrylate) nanoparticles in healthy rats and rats with intracranial glioblastoma.

Polysorbate 80-coated poly(butyl cyanoacrylate) nanoparticles (NP) were shown to enable the transport of a number of drugs including the anti-tumour antibiotic doxorubicin (DOX) across the blood-brain barrier (BBB) to the brain after intravenous administration and to considerably reduce the growth of brain tumours in rats. The objective of the present study was to evaluate the acute toxicity of DOX associated with polysorbate 80-coated NP in healthy rats and to establish a therapeutic dose range for this formulation in rats with intracranially implanted 101/8 glioblastoma. Single intravenous administration of empty poly(butyl cyanoacrylate) NP in the dose range 100-400 mg/kg did not cause mortality within the period of observation. NP also did not affect body weight or weight of internal organs. Association of DOX with poly(butyl cyanoacrylate) NP did not produce significant changes of quantitative parameters of acute toxicity of the anti-tumour agent. Likewise, the presence of polysorbate 80 in the formulations was not associated with changes in toxicity compared with free or nanoparticulate drug. Dose regimen of 3x1.5 mg/kg on days 2, 5, 8 after tumour implantation did not cause drug-induced mortality. The results in tumour-bearing rats were similar to those in healthy rats. These results demonstrate that the toxicity of DOX bound to NP was similar or even lower than that of free DOX.

Animals↗

PubMed2000

Relationship between polysorbate 80 solubilization descriptors and octanol-water partition coefficients of drugs.

The molar solubilization capacities (kappa) and the molar micelle-water partition coefficients (K(M)(N)) in Polysorbate 80 of several drugs (including barbiturates, steroids, and benzoic acid derivatives) are related to their log octanol-water partition coefficients (logP). Both kappa and K(M)(N) values were calculated from solubility versus Polysorbate 80 concentration profiles, which were either experimentally determined or obtained from the literature. There is a linear relationship between logP of the tested compounds and the logarithm of the molar micelle-water partition coefficient (logK(M)(N)). On the other hand molar solubilization capacities are nearly independent of logP. It is shown that the ability of Polysorbate 80 to solubilize a drug can be predicted from its logP value.

Octanols↗

PubMed1998

Quantitative determination of polysorbate 20 in nasal pharmaceutical preparations by high-performance liquid chromatography.

A specific reverse-phase HPLC method has been developed for the quantitative determination of polysorbate 20 in various compositions of nasal solutions. This method is based on the acidic hydrolysis of the sorbitan laurate ester followed by the HPLC determination of the free lauric acid. Using this method, polysorbate 20 can effectively be separated and quantitatively determined in matrices containing a wide variety of preservatives, surfactants, and viscosity agents. Sample preparation involves a one-step hydrolysis with sulfuric acid and then a dilution with acetonitrile, prior to injection. The sample is analyzed on a 5-microm octadecylsilane reverse-phase column with a mobile phase of acetonitrile: 0.025 M aqueous di-Sodium hydrogen phosphate, pH = 2.8 (75:25). The column effluent is monitored by UV detection at 210 nm. The validity of the method has been verified with specificity, linearity, recovery, method- and system precisions data. The method is linear for polysorbate 20 from 2.5 to 125 mg ml(-1) range. The limit of detection and limit of quantitation are 0.41 and 0.61 mg ml(-1), respectively.

Administration, Intranasal↗

PubMed1979

Additivity of action between polysorbate 80 and polymyxin B towards spheroplasts of Pseudomonas aeruginosa NCTC 6750.

When polymyxin B and polysorbate 80 were used together against spheroplasts of Pseudomonas aeruginosa, the activities were found to be additive. These substances have previously been reported to act synergistically against P. aeruginosa, but little or no intrinsic activity towards intact cells has been attributed to polysorbate 80. We suggest that in addition to enhancing polymyxin B penetration to the cytoplasmic membrane, polysorbate 80 may also act as an antimicrobial agent when polymyxin-induced damage to the outer membrane facilitates the surfactant's passage through the cell envelope.

Polyethylene Glycols↗

PubMed1986

Polysorbate 20 as a drug release regulator in ethyl cellulose film coatings.

Tablet coatings of hydrophobic ethyl cellulose have been made more hydrophilic by the addition of a non-ionic surfactant, polysorbate (Tween) 20, to the film. As its content increased, so did the release of sodium salicylate from the coated tablets. With a certain content of surfactant and specific thickness of the tablet coat, zero order release kinetics were observed. Leaching of the polysorbate 20 occurred from all formulations. Scanning and transmission electron micrographs showed that the structure of the coats consisted of several layers parallel to the tablet surface. Polysorbate 20 was seen as small drops in some coats.

Cellulose↗

PubMed1989

Solubilization of indomethacin by polysorbate 80 in mixed water-sorbitol solvents.

The effect of indomethacin on the micellar properties of the non-ionic surfactant, polysorbate 80, in water-sorbitol mixtures containing up to 25% w/v sorbitol has been investigated by light scattering, photon correlation spectroscopy and viscometric techniques. The molecular weight of polysorbate 80 micelles containing solubilized indomethacin increased linearly with increase of sorbitol concentration. Solubilization of indomethacin resulted in an increase of micellar weight due not only to the incorporation of solubilizate but also to an increase in the number of polysorbate molecules per micelle. The micelles in all systems were most satisfactorily represented as oblate ellipsoids, the asymmetry and hydration of which increased with increase of sorbitol concentration. Indomethacin solubilization caused a restructuring of the micelle to produce a more symmetrical micelle of increased hydration.

Indomethacin↗

PubMedDate not supplied

The effect of niosomes and polysorbate 80 on the metabolism and excretion of methotrexate in the mouse.

The effect of non-ionic surfactant vesicle (niosome) encapsulation on the metabolism and urinary and faecal excretion of methotrexate (MTX) in mice has been studied following oral and intravenous administration, and compared with the effects of co-administration of free drug and polysorbate 80, which does not form vesicles. Niosome entrapment reduces the excretion of MTX into urine and bile whereas polysorbate 80 increases its excretion. Monitoring of the levels of MTX and its 7-hydroxy metabolite indicates that entrapped MTX is protected from rapid metabolism in vivo, particularly in niosomes but to a small degree in the micellar systems formed by polysorbate.

Administration, Oral↗

PubMed2002

Influence of some polysorbates on hydrocortisone release from hydrophilic gels considered as two-compartment models.

Hydrocortisone release from hydrogels containing of 1% and 3% polysorbate 20 or polysorbate 80, in the presence of 1,2-propylene glycol or PEG 200 has two stages. In the first one the release rates are higher than those of the second stage. Half-release times in the first stage are in the range 0.31 h to 0.48 h and in the second stage 16.65 h to 23.22 h. Hydrocortisone release from the gels containing of 1% to 3% of polysorbate 21 or 81, in the presence of 1,2-propylene glycol or PEG 200 conform to second order kinetics. Release rates in this stage are in the range from 3.80 x 10(-4)%.h-1 to 5.97 x 10(-4)%.h-1.

Anti-Inflammatory Agents↗

PubMed2006

Enhanced delivery of etoposide to Dalton's lymphoma in mice through polysorbate 20 micelles.

The study evaluates the possibility of enhancing uptake of etoposide (topoisomerase II inhibitor) by tumor when delivered through polysorbate 20 micelles. The micelle formation was ascertained by determining the critical micellar concentration (CMC) with a du Nouy ring tensiometer and by size measurement using dynamic light scattering. Addition of 5% ethanol decreased the CMC of Polysorbate 20 (from 5.0 x 10(-5) to 4.54 x 10(-5) mol L(-1)). Etoposide (ET) and etoposide loaded polysorbate 20 micelles (EPM) were radiolabeled with 99mTc by the reduction method using stannous chloride. Labeling parameters were optimized to obtain high labeling efficiency. The diethylenetriaminepentaacetic acid and cysteine challenge tests showed very low transchelation of 99mTc-ET and 99mTc-EPM complexes indicating their in vitro stability. The complexes also exhibited serum stability assessed by ascending thin layer chromatography. Subcutaneous injection of EPM resulted in significantly higher tumor uptake ( 100 folds compared to ET 6 h post injection) (p < 0.001) and prolonged tumor retention. Tumor uptake was also confirmed by gamma imaging studies. EPM exhibited relatively high brain concentrations ( 7 fold 24 h post injection) compared to ET, suggesting the potential use of EPM in the treatment of brain malignancies.

Animals↗

PubMed1985

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↗

PubMed1986

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↗