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| Product Name: | Polyethylene Glycol | | Synonyms: | 2-ethanediyl),.alpha.-hydro-.omega.-hydroxy-Poly(oxy-1;Alcox E 160;Alcox E 30;Poly(ethylene oxide),approx. M.W. 900,000;POLYETHYLENE GLYCOL 1550PRACT.;Poly(ethylene glycol),Macrogol 35,000, PEG;Poly(ethylene glycol),Macrogol 3,000, PEG;Poly(ethylene glycol),Macrogol 300, PEG | | CAS: | 25322-68-3 | | MF: | N/A | | MW: | 0 | | EINECS: | 500-038-2 | | Product Categories: | Gas Chromatography;Packed GC;Stationary Phases;Cosmetic Ingredients & Chemicals;Polydispersed PEG;Optimization Reagents;Protein Structural Analysis;X-Ray Crystallography;Polymers;polymeride;Poly(ethylene glycol) (PEG) and PEG Solutions;Poly(ethylene glycol) and Oligo(ethylene glycol);Essential Chemicals;Inorganic Salts;Materials Science;Poly(ethylene glycol) and Poly(ethylene oxide);Polymer Science;Research Essentials;Solutions and Reagents;Homobifunctional PEG;peg;25322-68-3 | | Mol File: | 25322-68-3.mol |  |
| | Polyethylene Glycol Chemical Properties |
| Melting point | 64-66 °C | | Boiling point | >250°C | | density | 1.27 g/mL at 25 °C | | vapor density | >1 (vs air) | | vapor pressure | <0.01 mm Hg ( 20 °C) | | refractive index | n20/D 1.469 | | Fp | 270 °C | | storage temp. | 2-8°C | | solubility | H2O: 50 mg/mL, clear, colorless | | form | waxy solid | | Specific Gravity | 1.128 | | color | White to very pale yellow | | PH | 5.5-7.0 (25℃, 50mg/mL in H2O) | | Water Solubility | Soluble in water. | | Sensitive | Hygroscopic | | λmax | λ: 260 nm Amax: 0.6
λ: 280 nm Amax: 0.3 | | Merck | 14,7568 | | Stability: | Stable. Incompatible with strong oxidizing agents. | | LogP | -0.698 at 25℃ | | NIST Chemistry Reference | Polyethylene glycol(25322-68-3) | | EPA Substance Registry System | Polyethylene glycol (25322-68-3) |
| | Polyethylene Glycol Usage And Synthesis |
| Chemical properties | Polyethylene glycol is a polymer which is hydrolyzed by ethylene oxide. It has no toxicity and irritation. It is widely used in various pharmaceutical preparations. The toxicity of low molecular weight polyethylene glycol is relatively large. In general, the toxicity of diols is very low. Topical application of polyethylene glycol, especially mucosal drug, can cause irritant pain. In topical lotion, this product can increase the flexibility of the skin, and has a similar moisturizing effect with glycerin. Diarrhoea can occur in large doses of oral administration. In injection, the maximum polyethylene glycol 300 concentration is about 30% (V/V). Hemolysis could occur when the concentration is more than 40% (V/V).
| | Application in biomedicine | Polyethylene glycol is also known as polyoxirane (PEO). It is a linear polyether obtained by ring opening polymerization of ethylene oxide. The main uses in the field of biomedicine are as follows:
- Contact lens liquid. The viscosity of polyethylene glycol solution is sensitive to the shear rate and it is not easy for bacteria to grow on polyethylene glycol.
- Synthetic lubricants. The condensation polymer of ethylene oxide and water. It is a cream matrix for preparing water-soluble drugs. It can also be used as a solvent for acetylsalicylic acid and caffeine, which is difficult to dissolve in water.
- Drug sustained-release and immobilized enzyme carrier. The polyethylene glycol solution is applied to the outer layer of the pill to control the diffusion of drugs in the pill so as to improve the efficacy.
- Surface modification of medical polymer materials. The biocompatibility of medical polymer materials in contact with blood can be improved by adsorption, interception and grafting of two amphiphilic copolymers containing polyethylene glycol on the surface of medical polymers.
- It can make the membrane of the alkanol contraceptive pill.
- It can make hydrophilic anticoagulant polyurethane.
- Polyethylene glycol 4000 is an osmotic laxative. It can increase osmotic pressure and absorb moisture in the intestinal cavity, which makes the stool soften and increase in volume, resulting in bowel movement and defecation.
- Denture fixing agent. Peg nontoxic and gelatinous nature can be used as a component of denture fixer.
- PEG 4000 and PEG 6000 are commonly used to promote cell fusion or protoplast fusion and help organisms (such as yeasts) to take DNA in transformation. PEG absorbs water from the solution, so it is also used to concentrate the solution.
| | Description | Polyethylene glycols are a family of linear polymers formed
by a base-catalyzed condensation reaction with repeating
ethylene oxide units being added to ethylene. The molecular
formula is (C2H4O)multH2O where mult denotes the average
number of oxyethylene groups. The molecular weight can
range from 200 to several million corresponding to the
number of oxyethylene groups. The higher-molecular-weight
materials (100 000 to 5 000 000) are also referred to as
polyethylene oxides. The average molecular weight of any
specific polyethylene glycol product falls within quite narrow
limits (°5%). The number of ethylene oxide units or their
approximate molecular weight (e.g., PEG-4 or PEG-200)
commonly designates the nomenclature of specific polyethylene
glycols. Polyethylene glycols with amolecular weight
less than 600 are liquid, whereas those of molecular weight
1000 and above are solid. These materials are nonvolatile,
water-soluble, tasteless, and odorless. They are miscible with
water, alcohols, esters, ketones, aromatic solvents, and chlorinated
hydrocarbons, but immiscible with alkanes, paraffins,
waxes, and ethers. | | Chemical Properties | The USP32–NF27 describes polyethylene glycol as being an
addition polymer of ethylene oxide and water. Polyethylene glycol
grades 200–600 are liquids; grades 1000 and above are solids at
ambient temperatures.
Liquid grades (PEG 200–600) occur as clear, colorless or slightly
yellow-colored, viscous liquids. They have a slight but characteristic
odor and a bitter, slightly burning taste. PEG 600 can occur as a
solid at ambient temperatures.
Solid grades (PEG>1000) are white or off-white in color, and
range in consistency from pastes to waxy flakes. They have a faint,
sweet odor. Grades of PEG 6000 and above are available as freeflowing
milled powders. | | Chemical Properties | White waxy crystalline flakes | | Originator | MiraLax ,Braintree Laboratories | | Uses | polyethylene glycol (PEG) is a binder, solvent, plasticizing agent, and softener widely used for cosmetic cream bases and pharmaceutical ointments. Pegs are quite humectant up to a molecular weight of 500. Beyond this weight, their water uptake diminishes. | | Uses | nonionic emulsifier | | Uses | Poly(ethylene Glycol) molecules of approximately 2000 monomers. Poly(ethylene Glycol) is used in various applications from industrial chemistry to biological chemistry. Recent research has shown PEG m
aintains the ability to aid the spinal cord injury recovery process, helping the nerve impulse conduction process in animals. In rats, it has been shown to aid in the repair of severed sciatic axons,
helping with nerve damage recovery. It is industrially produced as a lubricating substance for various surfaces to reduce friction. PEG is also used in the preparation of vesicle transport systems in
with application towards diagnostic procedures or drug delivery methods. | | Uses | H2 histamine receptor antagonist, anti-ulcer agent | | Uses | A polymer used to precipitate proteins, viruses, DNA and RNA | | Uses | Polyethylene Glycol is a binder, coating agent, dispersing agent,
flavoring adjuvant, and plasticizing agent that is a clear, colorless,
viscous, hygroscopic liquid resembling paraffin (white, waxy, or
flakes), with a ph of 4.0–7.5 in 1:20 concentration. it is soluble in
water (mw 1,000) and many organic solvents. | | Uses | Used in conjunction with carbon black to form a conductive composite.1 Polymer nanospheres of poly(ethylene glycol) were used for drug delivery.2 | | Production Methods | Polyethylene glycol polymers are formed by the reaction of ethylene
oxide and water under pressure in the presence of a catalyst. | | Definition | Any of several condensa-tion polymers of ethylene glycol with thegeneral formula HOCH2(CH2OCH2)nCH2OH orH(OCH2CH2)nOH. Average molecular weightsrange from 200 to 6000. Properties vary with molec-ular weight. | | Preparation | The ring-opening polymerization of ethylene oxide is readily effected by a
variety of ionic reagents and several types of polymer have been prepared.
For commercial purposes, poly(ethylene oxide)s of low molecular weight and
of very high molecular weight are of interest.
(a) Low molecular weight polymers
Poly(ethylene oxide)s of low molecular weight, i.e. below about 3000, are
generally prepared by passing ethylene oxide into ethylene glycol at
120-150??C and about 0.3 MPa (3 atmospheres) pressure, using an alkaline
initiator such as sodium hydroxide. Anionic polymerization proceeds according to the following scheme:
20220127142458
The polymers produced by these methods are thus terminated mainly by
hydroxy groups (a few unsaturated end-groups are also formed) and are often
referred to as poly(ethylene glycol)s. Poly(ethylene glycol)s with molecular
weights in the range 200-600 are viscous liquids which find use as surfactants
in inks and paints and as humectants. At molecular weights above about 600,
poly(ethylene glycol)s are low-melting waxy solids, uses of which include
pharmaceutical and cosmetic bases, lubricants and mould release agents.
It may be noted that homogeneous cationic polymerization of ethylene
oxide also generally leads to low molecular weight products; typical initiators
include aluminium chloride, boron trifluoride and titanium tetrachloride.
Systems of this type are not utilized on a commercial scale.
(b) High molecular weight polymers
Poly(ethylene oxide)s of molecular weight ranging from about 100000 to
5 x 106 and above are available. Details of the techniques used to manufacture these polymers have not been disclosed, but the essential feature is the
use of (generally) heterogeneous initiator systems. Effective initiators are
mainly of two types, namely alkaline earth compounds (e.g. carbonates and
oxides of calcium, barium and strontium) and organometallic compounds
(e.g. aluminium and zinc alkyls and alkoxides, commonly with added coinitiators).
The precise modes of action of these initiators have not, as yet, been fully
resolved. However, it is now generally thought that polymerization occurs
through a co-ordinated anionic mechanism, in which the ethylene oxide is coordinated to the initiator through an unshared electron pair on the oxirane
oxygen atom:
Unlike the low molecular weight poly(ethylene oxide)s, the high molecular
weight polymers are tough and extensible. They are highly crystalline, with a
melting point of 66??C. Unlike most water-soluble polymers, the high molecular weight poly(ethylene oxide)s may be melt processed; they may be injection
moulded, extruded and calendered without difficulty.
Poly(ethylene oxide)s are soluble in an unusually broad range of solvents,
which includes water; chlorinated hydrocarbons such as carbon tetrachloride
and methylene dichloride; aromatic hydrocarbons such as benzene and
toluene; ketones such as acetone and methyl ethyl ketone; and alcohols such
as methanol and isopropanol. There is an upper temperature limit of solubility in water for the high molecular weight poly(ethylene oxide)s; this varies
with concentration and molecular weight but is usually between 90 and 100??C.
Water-solubility is due to the ability of the polyether to form hydrogen
bonds with water; these bonds are broken when the temperature is raised,
restoring the anhydrous polymer which is precipated from the solution.
High molecular weight poly(ethylene oxide)s find use as water-soluble
packaging films and capsules for such products as laundry powders, colour
concentrates, tablets and seeds. In solution, the polymers are used as thickeners in pharmaceutical and cosmetic preparations, textile sizes and latex
stabilizers. | | Indications | Polyethylene glycol (Miralax) is another osmotic
laxative that is colorless and tasteless once it is mixed. | | Manufacturing Process | Polyethylene glycol 3350 was obtained by polymerization of ethylene oxide in an autoclave at 80-100°C using as a catalyst dipotassium alcogolate of polyethylene glycol 400.
Dipotassium alcogolate of polyethylene glycol 400 was synthesized by a heating of the dry mixture of polyethylene glycol 400 and potassium hydroxide. The molecular weight of polymer was regulated by the ratio of monomer:catalyst. | | Brand name | Atpeg 4000 (ICI Americas). | | Therapeutic Function | Laxative | | General Description | Clear colorless viscous liquid. | | Air & Water Reactions | Water soluble. | | Reactivity Profile | Poly(ethylene glycol) is heat-stable and inert to many chemical agents; Poly(ethylene glycol) will not hydrolyze or deteriorate under normal conditions. Poly(ethylene glycol) has a solvent action on some plastics. | | Fire Hazard | Poly(ethylene glycol) is combustible. | | Flammability and Explosibility | Notclassified | | Pharmaceutical Applications | Polyethylene glycols (PEGs) are widely used in a variety of
pharmaceutical formulations, including parenteral, topical,
ophthalmic, oral, and rectal preparations. Polyethylene glycol has
been used experimentally in biodegradable polymeric matrices used
in controlled-release systems.
Polyethylene glycols are stable, hydrophilic substances that are
essentially nonirritant to the skin;They do not
readily penetrate the skin, although the polyethylene glycols are
water-soluble and are easily removed from the skin by washing,
making them useful as ointment bases.Solid grades are generally
employed in topical ointments, with the consistency of the base
being adjusted by the addition of liquid grades of polyethylene
glycol.
Mixtures of polyethylene glycols can be used as suppository
bases,for which they have many advantages over fats. For
example, the melting point of the suppository can be made higher to
withstand exposure to warmer climates; release of the drug is not
dependent upon melting point; the physical stability on storage is
better; and suppositories are readily miscible with rectal fluids.
Polyethylene glycols have the following disadvantages: they are chemically more reactive than fats; greater care is needed in
processing to avoid inelegant contraction holes in the suppositories;
the rate of release of water-soluble medications decreases with the
increasing molecular weight of the polyethylene glycol; and
polyethylene glycols tend to be more irritating to mucous
membranes than fats.
Aqueous polyethylene glycol solutions can be used either as
suspending agents or to adjust the viscosity and consistency of other
suspending vehicles. When used in conjunction with other
emulsifiers, polyethylene glycols can act as emulsion stabilizers.
Liquid polyethylene glycols are used as water-miscible solvents
for the contents of soft gelatin capsules. However, they may cause
hardening of the capsule shell by preferential absorption of moisture
from gelatin in the shell.
In concentrations up to approximately 30% v/v, PEG 300 and
PEG 400 have been used as the vehicle for parenteral dosage forms.
In solid-dosage formulations, higher-molecular-weight polyethylene
glycols can enhance the effectiveness of tablet binders and
impart plasticity to granules.However, they have only limited
binding action when used alone, and can prolong disintegration if
present in concentrations greater than 5% w/w. When used for
thermoplastic granulations,a mixture of the powdered constituents
with 10–15% w/w PEG 6000 is heated to 70–75°C. The
mass becomes pastelike and forms granules if stirred while cooling.
This technique is useful for the preparation of dosage forms such as
lozenges when prolonged disintegration is required.
Polyethylene glycols can also be used to enhance the aqueous
solubility or dissolution characteristics of poorly soluble compounds
by making solid dispersions with an appropriate polyethylene
glycol.Animal studies have also been performed using
polyethylene glycols as solvents for steroids in osmotic pumps.
In film coatings, solid grades of polyethylene glycol can be used
alone for the film-coating of tablets or can be useful as hydrophilic
polishing materials. Solid grades are also widely used as plasticizers
in conjunction with film-forming polymers.The presence of
polyethylene glycols in film coats, especially of liquid grades, tends
to increase their water permeability and may reduce protection
against low pH in enteric-coating films. Polyethylene glycols are
useful as plasticizers in microencapsulated products to avoid
rupture of the coating film when the microcapsules are compressed
into tablets.
Polyethylene glycol grades with molecular weights of 6000 and
above can be used as lubricants, particularly for soluble tablets. The
lubricant action is not as good as that of magnesium stearate, and
stickiness may develop if the material becomes too warm during
compression. An antiadherent effect is also exerted, again subject to
the avoidance of overheating.
Polyethylene glycols have been used in the preparation of
urethane hydrogels, which are used as controlled-release agents.
Polyethylene glycol has also been used in insulin-loaded microparticles
for the oral delivery of insulin;it has been used in
inhalation preparations to improve aerosolization;polyethylene
glycol nanoparticles have been used to improve the oral bioavailability
of cyclosporine;it has been used in self-assembled
polymeric nanoparticles as a drug carrier;and copolymer
networks of polyethylene glycol grafted with poly(methacrylic
acid) have been used as bioadhesive controlled drug delivery
formulations. | | Biochem/physiol Actions | Poly(ethylene glycol) (PEG) helps in the purification and crystal growth of proteins and nucleic acids. PEG also interacts with cell membrane, thereby allowing cell fusion. | | Safety Profile | When heated to
decomposition it emits acrid smoke and
irritating fumes. | | Safety | Polyethylene glycols are widely used in a variety of pharmaceutical
formulations. Generally, they are regarded as nontoxic and
nonirritant materials.
Adverse reactions to polyethylene glycols have been reported,
the greatest toxicity being with glycols of low molecular weight.
However, the toxicity of glycols is relatively low.
Polyethylene glycols administered topically may cause stinging,
especially when applied to mucous membranes. Hypersensitivity
reactions to polyethylene glycols applied topically have also been
reported, including urticaria and delayed allergic reactions.
The most serious adverse effects associated with polyethylene
glycols are hyperosmolarity, metabolic acidosis, and renal failure
following the topical use of polyethylene glycols in burn patients.
Topical preparations containing polyethylene glycols should therefore
be used cautiously in patients with renal failure, extensive
burns, or open wounds.
Oral administration of large quantities of polyethylene glycols
can have a laxative effect. Therapeutically, up to 4 L of an aqueous
mixture of electrolytes and high-molecular-weight polyethylene
glycol is consumed by patients undergoing bowel cleansing.
Liquid polyethylene glycols may be absorbed when taken orally,
but the higher-molecular-weight polyethylene glycols are not
significantly absorbed from the gastrointestinal tract. Absorbed
polyethylene glycol is excreted largely unchanged in the urine,
although polyethylene glycols of low molecular weight may be
partially metabolized.
The WHO has set an estimated acceptable daily intake of
polyethylene glycols at up to 10 mg/kg body-weight.
In parenteral products, the maximum recommended concentration
of PEG 300 is approximately 30% v/v as hemolytic effects have
been observed at concentrations greater than about 40% v/v | | Environmental Fate | Like other polymeric substances, polyethylene glycols are not
readily biodegradable, with reported 5-day biochemical oxygen
demand (BOD5) of 0–1%. However, owing to their hydrophilicity,
they have a low potential to bioaccumulate. | | storage | Polyethylene glycols are chemically stable in air and in solution, although grades with a molecular weight less than 2000 are hygroscopic. Polyethylene glycols do not support microbial growth, and they do not become rancid.
Polyethylene glycols and aqueous polyethylene glycol solutions can be sterilized by autoclaving, filtration, or gamma irradiation.
Sterilization of solid grades by dry heat at 150℃ for 1 hour may induce oxidation, darkening, and the formation of acidic degradation products. Ideally, sterilization should be carried out in an inert atmosphere. Oxidation of polyethylene glycols may also be inhibited by the inclusion of a suitable antioxidant.
If heated tanks are used to maintain normally solid polyethylene glycols in a molten state, care must be taken to avoid contamination with iron, which can lead to discoloration. The temperature must be kept to the minimum necessary to ensure fluidity; oxidation may occur if polyethylene glycols are exposed for long periods to temperatures exceeding 50℃. However, storage under nitrogen reduces the possibility of oxidation.
Polyethylene glycols should be stored in well-closed containers in a cool, dry place. Stainless steel, aluminum, glass, or lined steel containers are preferred for the storage of liquid grades. | | Purification Methods | PEG is available commercially as a powder or as a solution in various degrees of polymerization depending on the average molecular weight, e.g. PEG 400 and PEG 800 have average molecular weights of 400 and 800, respectively. They may be contaminated with aldehydes and peroxides. Solutions deteriorate in the presence of air due to the formation of these contaminants. Methods available for purification are as follows: Procedure A: A 40% aqueous solution of PEG 400 (2L, average molecular weight 400) is de-aerated under vacuum and made 10mM in sodium thiosulfate. After standing for 1hour at 25o, the solution is passed through a column (2.5x20cm) of mixed-bed R-208 resin which has a 5cm layer of Dowex 50-H+ at the bottom of the column. The column was previously flushed with 30% aqueous MeOH, then thoroughly with H2O. A flow rate of 1mL/minute is maintained by adjusting the fluid head. The first 200mL are discarded, and the effluent is then collected at an increased flow rate. The concentration of PEG solution is checked by density measurement, and it is stored (preferably anaerobically) at 15o. Procedure B: A solution of PEG 800 (500g in 805mL H2O) is made 1mM in H2SO4 and stirred overnight at 25o with 10g of treated Dowex 50-H+ (8% crosslinked, 20-50 mesh). The resin, after settling, is filtered off on a sintered glass funnel. The filtrate is treated at 25o with 1.5g of NaBH4 (added over a period of 1minute) in a beaker with tight but removable lid through which a propeller-type mechanical stirrer is inserted and continuously flushed with N2. After 15minutes, 15g of fresh Dowex 50-H+ are added, and the rate of stirring is adjusted to maintain the resin suspended. The addition of an equal quantity of Dowex 50-H+ is repeated and the reaction times are 30 and 40minutes. The pH of a 1 to 10 dilution of the reaction mixture should remain above pH 8 throughout. If it does not, more NaBH4 is added or the addition of Dowex 50-H+ is curtailed. (Some samples of PEG can be sufficiently acidic, at least after the hydrolysis treatment, to produce a pH that is too low for efficient reduction when the above ratio of NaBH4 to Dowex 50-H+ is used.) About 30minutes after the last addition of NaBH4, small amounts of Dowex 50-H+ (~0.2g) are added at 15minute intervals until the pH of a 1 to 10 dilution of the solution is less than 8. After stirring for an additional 15minutes the resin is allowed to settle, and the solution is transferred to a vacuum flask for brief de-gassing under a vacuum. The de-gassed solution is passed through a column of mixed-bed resin as in procedure A. The final PEG concentration would be about 40% w/v. Assays for aldehydes by the purpural method and of peroxides are given in the reference below. Treatment of Dowex 50-H+ (8% crosslinked, 20-50 mesh): The Dowex (500g) is suspended in excess 2N NaOH, and 3mL of liquid Br2 is stirred into the solution. After the Br2 has dissolved, the treatment is repeated twice, and then the resin is washed with 1N NaOH on a sintered glass funnel until the filtrate is colourless. The resin is then converted to the acid form (with dilute HCl, H2SO4 or AcOH as required) and washed thoroughly with H2O and sucked dry on the funnel. The treated resin can be converted to the Na salt and stored. [Ray & Purathingal Anal Biochem 146 307 1985.] | | Toxicity evaluation | Many years of human experience in the workplace and in the
use of consumer products containing polyethylene glycols have
not shown any adverse health effects, except in situations where
very high doses are administered to hypersusceptible individuals
or persons with underlying diseases. | | Incompatibilities | The chemical reactivity of polyethylene glycols is mainly confined to
the two terminal hydroxyl groups, which can be either esterified or
etherified. However, all grades can exhibit some oxidizing activity
owing to the presence of peroxide impurities and secondary
products formed by autoxidation.
Liquid and solid polyethylene glycol grades may be incompatible
with some coloring agents.
The antibacterial activity of certain antibiotics is reduced in
polyethylene glycol bases, particularly that of penicillin and
bacitracin. The preservative efficacy of the parabens may also be
impaired owing to binding with polyethylene glycols.
Physical effects caused by polyethylene glycol bases include
softening and liquefaction in mixtures with phenol, tannic acid, and
salicylic acid. Discoloration of sulfonamides and dithranol can also
occur, and sorbitol may be precipitated from mixtures. Plastics, such
as polyethylene, phenolformaldehyde, polyvinyl chloride, and cellulose-ester membranes (in filters) may be softened or dissolved
by polyethylene glycols. Migration of polyethylene glycol can occur
from tablet film coatings, leading to interaction with core
components. | | Regulatory Status | Included in the FDA Inactive Ingredients Database (dental
preparations; IM and IV injections; ophthalmic preparations; oral
capsules, solutions, syrups, and tablets; rectal, topical, and vaginal
preparations). Included in nonparenteral medicines licensed in the
UK. Included in the Canadian List of Acceptable Non-medicinal
Ingredients. |
| | Polyethylene Glycol Preparation Products And Raw materials |
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