POLYSORBATE 80

IDENTIFICATION AND USE: Polysorbate 80 is a common excipient and solubilizing agent used in the pharmaceutical industry. Polysorbate 80 (also known as polyoxyethylene-sorbitan-20 mono-oleate, or Tween 80) is used in the pharmaceutical and cosmetic industry in lotions, medical preparations (e.g., vitamin oils, vaccines, and intravenous preparations) and as an excipient in tablets.

A solubilizing agent acts as a surfactant and increases the solubility of one agent in another. A substance that would not normally dissolve in a particular solution is able to dissolve with the use of a solubilizing agent.

Polysorbate 80 is used as a solubilizing agent in IV formulations of the antiarrhythmic drug amiodarone. Rare case reports of liver toxicity have been published suggesting polysorbate 80 may contribute to liver toxicity with the IV formulation of amiodarone. The package labeling of amiodarone warns that polysorbate 80 is also known to leach DEHP (dioctyl phthalate) from PVC and dosing recommendations should be followed closely.

ANIMAL EXPOSURE/TOXICITY: Polyoxyethylene (20) sorbitan monooleate (polysorbate 80, Tween 80), a surfactant, has been widely used as a solvent for pharmacological experiments. In the present study, polysorbate 80 was found to have toxicity of a low order in both the mice and rats when given by i.p. and p.o. routes.

It produced mild to moderate depression of the central nervous system with a marked reduction in locomotor activity and rectal temperature, exhibited ataxia and paralytic activity and potentiated the pentobarbital sleeping time. On intravenous administration in dogs, it had a dose-dependent hypotensive effect. Polysorbate 80 did not have a direct stimulant or relaxant effect on either guinea pig ileum or rat uterus, however, it antagonised the contractions induced by acetylcholine, histamine, barium, 5-hydroxytryptamine and carbachol in a dose-dependent manner. A direct relaxant effect was observed on rabbit jejunum.

A dose-dependent myocardial depressant effect was observed on guinea pig and rabbit paired atrial preparations. On the electrically-driven guinea pig left atrial preparation, polysorbate 80 exhibited a dose-dependent negative inotropic action. Polysorbate 80 did not induce diuresis in rats upto a dose of 2.5 ml/kg.

The results of the present study indicate that polysorbate 80 can neither be used as a solvent for isolated tissue experiments nor when considered for intravenous administration. However, polysorbate 80 can be employed safely as a vehicle for neuropsychopharmacological experiments in doses not exceeding 1 ml/kg.

HUMAN EXPOSURE/TOXICITY: Certain drugs such as dalargin, loperamide or tubocurarine are not transported across the blood-brain barrier (BBB) and therefore exhibit no effects on the central nervous system. However, effects on the central nervous system can be observed when these drugs are loaded onto polybutylcyanoacrylate (PBCA)-nanoparticles and coated with polysorbate 80.

The mechanism by which these complexed nanoparticles cross the BBB and exhibit their effects has not been elucidated. Cultured microvessel brain endothelial cells of human and bovine origin were used as an in vitro model for the BBB to gain further insight into the mechanism of uptake of nanoparticles. With cells from these species we were able to show that polysorbate 80-coated nanoparticles were taken up by brain endothelial cells much more rapidly and in significantly higher amounts (20-fold) than uncoated nanoparticles.

The process of uptake was followed by fluorescence and confocal laser scanning microscopy. The results demonstrate that the nanoparticles are taken up by cells and that this uptake occurs via an endocytotic mechanism.

ADVERSE EFFECTS: side effects include abdominal or stomach pain, accumulation of pus, arm, back, or jaw pain, blurred vision, breathing problems (irregular, noisy, or trouble when resting), chest pain, discomfort, tightness, or heaviness, chills, confusion, cough producing mucus, decrease in the amount of urine, diarrhea, dilated neck veins, dizziness, fainting, or lightheadedness, dry mouth, fast, slow, or irregular heartbeat, fatigue or tiredness (extreme or unusual), fever, headache, nausea, pain, tenderness, swelling, or warmth over injection site, pounding in the ears, rapid breathing, rapid or pounding pulse, shortness of breath, skin discoloration at the injection site, sunken eyes, sweating, swelling of the ankles, face, fingers, feet, hands, or lower legs, thirst, trouble with breathing, unconsciousness, vomiting, weight gain, wheezing, wrinkled skin, anxiety, convulsions, difficulty with speaking (slow speech or unable to speak), double vision, trouble with thinking, trouble with walking, unable to move the arms, legs, or face muscles (including numbness and tingling), fever and sore throat, hives, itching, pale skin, skin rash, unusual tiredness or weakness, constipation, general feeling of discomfort or illness, lack or loss of strength, loss of appetite, muscle aches, pains, or stiffness, pain in the joints, runny nose, shivering, sneezing, trouble with sleeping.

Clinical studies have shown darbepoetin alfa (albumin) to increase the risk of serious side effects (eg, blood clots, stroke, heart attack, heart failure) and death in some cases. It has also been shown to increase the risk of tumor growth in patients with advanced cancer.

FOUND IN THE FOLLOWING VACCINES: HEP A (HAVRIX), HEP A + HEP B( TWINRIX), DTAP + IPV + HIB (PENTACEL), DTAP (INFANRIX), HPV (GARDASIL), INFLUENZA (FLULAVAL), PNEUMOCOCCAL (PCV13- PREVNAR), ROTAVIRUS (ROTATEQ), TDAP (BOOSTRIX), DTAP + IPV (KINRIX), DTAP + HEP B + IPV (PEDIARIX)