Polyethylene glycol = PEG
CAS number: 25322-68-3
EC / List number: 500-038-2
E number: E1521 (additional chemicals)
Polyethylene glycol is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine.
The structure of PEG is commonly expressed as H−(O−CH2−CH2)n−OH.
Polyethylene glycol (PEG) is a versatile polyether being utilized in various applications.
Polyethylene glycol (PEG) is a product with industrial and pharmaceutical uses.
Since many Polyethylene glycol compounds are hydrophilic, industrially, they are utilized in cosmetic products as surfactants, emulsifiers, cleansing agents, humectants, and skin conditioners
Polyethylene glycol (PEG) is a hydrophilic polymer of ethylene oxide.
Polyethylene oxide (PEO) is another name for PEG.
Typically, ethylene oxide macromolecules with molecular weights less than 20,000 g/mol are called PEG, while those having values above 20,000 g/mol are named PEO.
It is reported that Polyethylene glycol is soluble in water, ethanol, acetonitrile, benzene, and dichloromethane, while it is insoluble in diethyl ether and hexane.
Polyethylene glycol is available in different structures such as branched, star, and comb-like macromolecules.
PEGylation is an attractive process in which Polyethylene glycol is bonded to another molecule, which is promising in therapeutic methods.
Polyethylene glycol (PEG) is a hydrophilic polyether compound being used in areas from industrial manufacturing to medicine.
Other chemically synonymous molecules of Polyethylene glycol are also known as polyethylene oxide (PEO) and polyoxyethylene (POE).
Polyethylene glycol (PEG) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine.
Polyethylene glycol is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular weight.
Identifiers of Polyethylene glycol:
CAS Number: 25322-68-3
Abbreviations: PEG
ChEMBL: ChEMBL1201478
ChemSpider: none
ECHA InfoCard: 100.105.546
E number: E1521 (additional chemicals)
UNII: 3WJQ0SDW1A check
CompTox Dashboard (EPA): DTXSID4027862
Tetradecyl tetradecanoate is a 100% natural vegetable derived ester utilizing only the Myristic fatty acids.
KEYWORDS:
25322-68-3, 500-038-2, PEG, E1521, POLYETHYLENE GLYCOL 200 USP , POLYETHYLENE GLYCOL 300, POLYETHYLENE GLYCOL 400, POLYETHYLENE GLYCOL 600, POLYETHYLENE GLYCOL 800, POLYETHYLENE GLYCOL 1000
Uses of Polyethylene glycol:
Medical uses of Polyethylene glycol:
Pharmaceutical-grade Polyethylene glycol is used as an excipient in many pharmaceutical products, in oral, topical, and parenteral dosage forms.
Polyethylene glycol is the basis of a number of laxatives (as MiraLax).
Whole bowel irrigation with polyethylene glycol and added electrolytes is used for bowel preparation before surgery or colonoscopy.
Polyethylene glycol is used in medicines for treating disimpaction and maintenance therapy for children with constipation.
When attached to various protein medications or drug carriers, polyethylene glycol of suitable length slows down their clearance from the blood.
The possibility that Polyethylene glycol could be used to fuse axons is being explored by researchers studying peripheral nerve and spinal cord injury.
An example of Polyethylene glycol hydrogels (see Biological uses section) in a therapeutic has been theorized by Ma et al.
They propose using the hydrogel to address periodontitis (gum disease) by encapsulating stem cells in the gel that promote healing in the gums.
The gel and encapsulated stem cells was to be injected to the site of disease and crosslinked to create the microenvironment required for the stem cells to function.
PEGylation of adenoviruses for gene therapy can help prevent adverse reactions due to pre-existing adenovirus immunity.
A PEGylated lipid is used as an excipient in both the Moderna and Pfizer–BioNTech vaccines for SARS-CoV-2.
Both RNA vaccines consist of messenger RNA, or mRNA, encased in a bubble of oily molecules called lipids.
Proprietary lipid technology is used for each. In both vaccines, the bubbles are coated with a stabilizing molecule of polyethylene glycol.
As of December 2020 there is some concern that PEG could trigger allergic reaction, and in fact allergic reactions are the driver for both the United Kingdom and Canadian regulators to issue an advisory, noting that: two "individuals in the U.K. ... were treated and have recovered" from anaphylactic shock.
As of 18 December, the US CDC stated that in their jurisdiction six cases of "severe allergic reaction" had been recorded from more than 250,000 vaccinations, and of those six only one person had a "history of vaccination reactions".
Chemical uses of Polyethylene glycol:
Because PEG is a hydrophilic molecule, it has been used to passivate microscope glass slides for avoiding non-specific sticking of proteins in single-molecule fluorescence studies.
Polyethylene glycol has a low toxicity and is used in a variety of products.
The polymer is used as a lubricating coating for various surfaces in aqueous and non-aqueous environments.
Since Polyethylene glycol is a flexible, water-soluble polymer, it can be used to create very high osmotic pressures (on the order of tens of atmospheres).
Polyethylene glycol also is unlikely to have specific interactions with biological chemicals.
These properties make Polyethylene glycol one of the most useful molecules for applying osmotic pressure in biochemistry and biomembranes experiments, in particular when using the osmotic stress technique.
Polyethylene glycol is also commonly used as a polar stationary phase for gas chromatography, as well as a heat transfer fluid in electronic testers.
Polyethylene glycol is frequently used to preserve waterlogged wood and other organic artifacts that have been salvaged from underwater archaeological contexts, as was the case with the warship Vasa in Stockholm, and similar cases.
It replaces water in wooden objects, making the wood dimensionally stable and preventing warping or shrinking of the wood when it dries.
In addition, Polyethylene glycol is used when working with green wood as a stabilizer, and to prevent shrinkage.
Polyethylene glycol has been used to preserve the painted colors on Terracotta Warriors unearthed at a UNESCO World Heritage site in China.
These painted artifacts were created during the Qin Shi Huang (first emperor of China) era. Within 15 seconds of the terra-cotta pieces being unearthed during excavations, the lacquer beneath the paint begins to curl after being exposed to the dry Xi'an air.
The paint would subsequently flake off in about four minutes.
The German Bavarian State Conservation Office developed a PEG preservative that when immediately applied to unearthed artifacts has aided in preserving the colors painted on the pieces of clay soldiers.
Polyethylene glycol is often used (as an internal calibration compound) in mass spectrometry experiments, with its characteristic fragmentation pattern allowing accurate and reproducible tuning.
Polyethylene glycol derivatives, such as narrow range ethoxylates, are used as surfactants.
Polyethylene glycol has been used as the hydrophilic block of amphiphilic block copolymers used to create some polymersomes.
Polyethylene glycol is a component of the propellent used in UGM-133M Trident II Missiles, in service with the United States Navy.
Biological uses of Polyethylene glycol:
Polyethylene glycol can be modified and crosslinked into a hydrogel and used to mimic the extracellular matrix (ECM) environment for cell encapsulation and studies.
An example study was done using PEG-diacrylate hydrogels to recreate vascular environments with the encapsulation of endothelial cells and macrophages.
This model furthered vascular disease modeling and isolated macrophage phenotype's effect on blood vessels.
Polyethylene glycol is commonly used as a crowding agent in in vitro assays to mimic highly crowded cellular conditions.
Polyethylene glycol is commonly used as a precipitant for plasmid DNA isolation and protein crystallization. X-ray diffraction of protein crystals can reveal the atomic structure of the proteins.
Polyethylene glycol is used to fuse two different types of cells, most often B-cells and myelomas in order to create hybridomas.
César Milstein and Georges J. F. Köhler originated this technique, which they used for antibody production, winning a Nobel Prize in Physiology or Medicine in 1984.
Polymer segments derived from PEG polyols impart flexibility to polyurethanes for applications such as elastomeric fibers (spandex) and foam cushions.
In microbiology, Polyethylene glycol precipitation is used to concentrate viruses.
Polyethylene glycol is also used to induce complete fusion (mixing of both inner and outer leaflets) in liposomes reconstituted in vitro.
Gene therapy vectors (such as viruses) can be PEG-coated to shield them from inactivation by the immune system and to de-target them from organs where they may build up and have a toxic effect.
The size of the Polyethylene glycol polymer has been shown to be important, with larger polymers achieving the best immune protection.
Polyethylene glycol is a component of stable nucleic acid lipid particles (SNALPs) used to package siRNA for use in vivo.
In blood banking, Polyethylene glycol is used as a potentiator to enhance detection of antigens and antibodies.
When working with phenol in a laboratory situation, PEG 300 can be used on phenol skin burns to deactivate any residual phenol.
In biophysics, polyethylene glycols are the molecules of choice for the functioning ion channels diameter studies, because in aqueous solutions they have a spherical shape and can block ion channel conductance.
Commercial uses of Polyethylene glycol:
Polyethylene glycol is the basis of many skin creams (as cetomacrogol) and personal lubricants (frequently combined with glycerin).
Polyethylene glycol is used in a number of toothpastes as a dispersant. In this application, it binds water and helps keep xanthan gum uniformly distributed throughout the toothpaste.
Polyethylene glycol is also under investigation for use in body armor, and in tattoos to monitor diabetes.
In low-molecular-weight formulations (e.g. PEG 400), it is used in Hewlett-Packard designjet printers as an ink solvent and lubricant for the print heads.
Polyethylene glycol is also used as an anti-foaming agent in food and drinks – its INS number is 1521 or E1521 in the EU.
Industrial uses of Polyethylene glycol:
A nitrate ester-plasticized polyethylene glycol (NEPE-75) is used in Trident II submarine-launched ballistic missile solid rocket fuel.
Dimethyl ethers of Polyethylene glycol are the key ingredient of Selexol, a solvent used by coal-burning, integrated gasification combined cycle (IGCC) power plants to remove carbon dioxide and hydrogen sulfide from the syngas stream.
Polyethylene glycol has been used as the gate insulator in an electric double-layer transistor to induce superconductivity in an insulator.
Polyethylene glycol is also used as a polymer host for solid polymer electrolytes.
Although not yet in commercial production, many groups around the globe are engaged in research on solid polymer electrolytes involving Polyethylene glycol, with the aim of improving their properties, and in permitting their use in batteries, electro-chromic display systems, and other products in the future.
Polyethylene glycol is injected into industrial processes to reduce foaming in separation equipment.
Polyethylene glycol is used as a binder in the preparation of technical ceramics.
Polyethylene glycol was used as an additive to silver halide photographic emulsions.
Entertainment uses of Polyethylene glycol:
Polyethylene glycol is used to extend the size and durability of very large soap bubbles.
Polyethylene glycol is the main ingredient in many personal lubricants. (Not to be confused with propylene glycol.)
Polyethylene glycol is the main ingredient in the paint (known as "fill") in paintballs.
Health effects of Polyethylene glycol:
Polyethylene glycol is considered biologically inert and safe by the FDA.
However, a growing body of evidence shows the existence of a detectable level of anti-PEG antibodies in approximately 72% of the population, never treated with PEGylated drugs, based on plasma samples from 1990 to 1999.
Due to its ubiquity in a multitude of products and the large percentage of the population with antibodies to PEG, hypersensitive reactions to PEG are an increasing concern.
Allergy to Polyethylene glycol is usually discovered after a person has been diagnosed with an allergy to an increasing number of seemingly unrelated products, including processed foods, cosmetics, drugs, and other substances that contain PEG or were manufactured with PEG.
Available forms and nomenclature of Polyethylene glycol:
PEG, PEO, and POE refer to an oligomer or polymer of ethylene oxide.
The three names are chemically synonymous, but historically Polyethylene glycol is preferred in the biomedical field, whereas PEO is more prevalent in the field of polymer chemistry.
Because different applications require different polymer chain lengths, Polyethylene glycol has tended to refer to oligomers and polymers with a molecular mass below 20,000 g/mol, PEO to polymers with a molecular mass above 20,000 g/mol, and POE to a polymer of any molecular mass.
Polyethylene glycols are prepared by polymerization of ethylene oxide and are commercially available over a wide range of molecular weights from 300 g/mol to 10,000,000 g/mol.
PEG and PEO are liquids or low-melting solids, depending on their molecular weights.
While PEG and PEO with different molecular weights find use in different applications, and have different physical properties (e.g. viscosity) due to chain length effects, their chemical properties are nearly identical.
Different forms of PEG are also available, depending on the initiator used for the polymerization process – the most common initiator is a monofunctional methyl ether PEG, or methoxypoly(ethylene glycol), abbreviated mPEG.
Lower-molecular-weight PEGs are also available as purer oligomers, referred to as monodisperse, uniform, or discrete.
Very high-purity PEG has recently been shown to be crystalline, allowing determination of a crystal structure by x-ray crystallography.
Since purification and separation of pure oligomers is difficult, the price for this type of quality is often 10–1000 fold that of polydisperse PEG.
Polyethylene glycols are also available with different geometries.
Branched Polyethylene glycols have three to ten PEG chains emanating from a central core group.
Star Polyethylene glycols have 10 to 100 PEG chains emanating from a central core group.
Comb Polyethylene glycols have multiple PEG chains normally grafted onto a polymer backbone.
The numbers that are often included in the names of PEGs indicate their average molecular weights (e.g. a PEG with n = 9 would have an average molecular weight of approximately 400 daltons, and would be labeled PEG 400).
Most Polyethylene glycols include molecules with a distribution of molecular weights (i.e. they are polydisperse).
The size distribution can be characterized statistically by its weight average molecular weight (Mw) and its number average molecular weight (Mn), the ratio of which is called the polydispersity index (ĐM).
Mw and Mn can be measured by mass spectrometry.
PEGylation is the act of covalently coupling a PEG structure to another larger molecule, for example, a therapeutic protein, which is then referred to as a PEGylated protein.
PEGylated interferon alfa-2a or alfa-2b are commonly used injectable treatments for hepatitis C infection.
Polyethylene glycol is soluble in water, methanol, ethanol, acetonitrile, benzene, and dichloromethane, and is insoluble in diethyl ether and hexane.
Polyethylene glycol is coupled to hydrophobic molecules to produce non-ionic surfactants.
Polyethylene glycols potentially contain toxic impurities, such as ethylene oxide and 1,4-dioxane.
Ethylene glycol and its ethers are nephrotoxic if applied to damaged skin.
Polyethylene oxide (PEO, Mw 4 kDa) nanometric crystallites (4 nm)
Polyethylene glycol and related polymers (PEG phospholipid constructs) are often sonicated when used in biomedical applications.
However, as reported by Murali et al., PEG is very sensitive to sonolytic degradation and PEG degradation products can be toxic to mammalian cells.
It is, thus, imperative to assess potential PEG degradation to ensure that the final material does not contain undocumented contaminants that can introduce artifacts into experimental results.
They vary in consistency from liquid to solid, depending on the molecular weight, as indicated by a number following the name.
They are used commercially in numerous applications, including foods, in cosmetics, in pharmaceutics, in biomedicine, as dispersing agents, as solvents, in ointments, in suppository bases, as tablet excipients, and as laxatives.
Some specific groups are lauromacrogols, nonoxynols, octoxynols, and poloxamers.
Macrogol, MiraLax, GoLytely, Colace used as a laxative, is a form of polyethylene glycol.
The name may be followed by a number which represents the average molecular weight (e.g. macrogol 3350, macrogol 4000 or macrogol 6000).
Production of Polyethylene glycol:
Polyethylene glycol 4000, pharmaceutical quality
The production of polyethylene glycol was first reported in 1859.
Both A. V. Lourenço and Charles Adolphe Wurtz independently isolated products that were polyethylene glycols.
Polyethylene glycol is produced by the interaction of ethylene oxide with water, ethylene glycol, or ethylene glycol oligomers.
The reaction is catalyzed by acidic or basic catalysts.
Ethylene glycol and its oligomers are preferable as a starting material instead of water, because they allow the creation of polymers with a low polydispersity (narrow molecular weight distribution).
Polymer chain length depends on the ratio of reactants.
HOCH2CH2OH + n(CH2CH2O) → HO(CH2CH2O)n+1H
Depending on the catalyst type, the mechanism of polymerization can be cationic or anionic.
The anionic mechanism is preferable because it allows one to obtain PEG with a low polydispersity.
Polymerization of ethylene oxide is an exothermic process.
Overheating or contaminating ethylene oxide with catalysts such as alkalis or metal oxides can lead to runaway polymerization, which can end in an explosion after a few hours.
Polyethylene oxide, or high-molecular-weight polyethylene glycol, is synthesized by suspension polymerization.
It is necessary to hold the growing polymer chain in solution in the course of the polycondensation process.
The reaction is catalyzed by magnesium-, aluminium-, or calcium-organoelement compounds.
To prevent coagulation of polymer chains from solution, chelating additives such as dimethylglyoxime are used.
Alkaline catalysts such as sodium hydroxide (NaOH), potassium hydroxide (KOH), or sodium carbonate (Na2CO3) are used to prepare low-molecular-weight polyethylene glycol.
The structure of Polyethylene glycol is commonly expressed as H−(O−CH2−CH2)n−OH
NAMES FOR POLYETHYLENE GLYCOL / MACROGOLS / PEGs
After the word Polyethylene glycol the number indicates the mean molecular weight of the polymer.
For liquid / waxy Polyethylene glycols no additional descriptor is used, with the exception of Polyethylene glycol 200 USP.
The capital letters USP indicate that this special grade of Polyethylene glycol 200 complies with the requirements for mono and diethylene glycol of the USP/NF.
For solid types the capital letter following the molecular weight number indicates the physical form of the material:
S ( German Schuppen = flakes),
P (powder, milled), PF (powder fine, milled) or
PS (powder, spray dried).
Bulk quantities of melt can be delivered in heated road tankers under the code FL.
MANUFACTURE of Polyethylene glycol:
Polyethylene glycols, also called macrogols in the European pharmaceutical industry, are manufactured by polymerization of ethylene oxide (EO) with either water, mono ethylene glycol or diethylene glycol as starting material, under alkaline catalysis.
After the desired molecular weight is reached (usually checked by viscosity measurements as in-process control) the reaction is terminated by neutralizing the catalyst with acid.
Normally lactic acid is used, but also acetic acid or others can also be used.
The result is a very simple chemical structure:
HO-[CH2-CH2-O]n-H, where (n) is the number of EO-units
NOMENCLATURE:
Although technically these products should be called polyethylene oxides, for products with mean molecular weights of 200 to 35000, the term polyethylene glycols is normally used to indicate the significant influence of the hydroxyl end groups on the chemical and physical properties of these molecules.
Only products made by polymerization of ethylene oxide in solvents, with molecular weights up to several millions, are called polyethylene oxides.
As an abbreviation for polyglycols, the term “PEG” is used, in combination with a numerical value.
Within the pharmaceutical industry, the number indicates the mean molecular weight, whereas in the cosmetic industry the number refers to the number (n) of EO-units in the molecule.
Since the molecular weight of ethylene oxide is 44, the average molecular weight values of PEGs are given as round values of n*44.
Unfortunately, the various pharmacopoeias use different nomenclature for some PEG molecular weights.
PROPERTIES of Polyethylene glycols:
Polyethylene glycols with a mean molecular weight up to 400 are non-volatile liquids at room temperature.
PEG 600 shows a melting range of about 17 to 22°C, so it may be liquid at room temperature but pasty at lower ambient temperatures, while PEGs with 800 to 2000 mean molecular weight are pasty materials with a low melting range.
Above a molecular weight of 3000, the polyethylene glycols are solids and are available not only in flaked form but also as powder.
Polyethylene glycols up to a molecular weight of 35000 are commercially available.
The hardness of Polyethylene glycols increases with increasing molecular weight, however the melting range goes up to a maximum value of about 60°C.
The most important property of all Polyethylene glycols is their solubility in water, making them ideally suited for use in countless different applications.
Liquid Polyethylene glycols up to PEG 600 are miscible with water in any ratio.
But even solid Polyethylene glycol grades have excellent solubility in water.
Although it falls slightly with increasing molar mass, even 50% (w / w) of a PEG 35000 can be dissolved.
The solubility and viscosity of the solutions is not affected by the presence of electrolytes, since Polyethylene glycols are nonionic substances.
Polyethylene glycols are quite soluble in hard water or in other aqueous solutions of various salts.
SURFACE TENSION of Polyethylene glycol:
The surface tension of the liquid PEGs 200 to 600 is about 47 mN/m at room temperature.
There is only a slight difference in the surface tension of liquid and solid PEGs in aqueous solutions; a 10% solution of PEG 400 has a value of 64 mN/m, while a 10% solution of PEG 4000 has a value of about 60 mN/m at 20°C.
PEGs possess no characteristic surfaceactive properties and can therefore not be included in the class surfactants.
Nevertheless, they frequently prove to be useful dispersing agents or solubilizers.
It is not possible to give an HLB value for PEGs.
LATENT HEAT OF FUSION:
The latent heat of fusion of the solid PEGs is 167-196 kJ/kg, depending to some extent on the degree of crystallinity.
SPECIFIC HEAT:
The specific heat (heat capacity) of the liquid PEGs at room temperature is about 2.1 kJ/kg K.
With rising temperature it increases steadily and at 120°C reaches about 2.5 kJ/kg K.
THERMAL CONDUCTIVITY:
For liquid PEG grades the thermal conductivity at room temperature is 0.23 W/m K. (Water: 0.6 W/m K).
COEFFICIENT OF THERMAL EXPANSION:
The coefficient of volumetric thermal expansion of liquid PEGs at 20°C is about 0.00073 K-1 and increases linearly up to 0.00080 K-1 at 160°C.
SOLUBILITY OF POLYETHYLENE GLYCOL IN WATER:
When liquid Polyethylene glycols are mixed with water, a volume contraction takes place.
When equal parts by weight PEG 400 and water are mixed together, this contraction amounts to about 2.5%.
At the same time a marked heat effect occurs.
The temperature rise taking place when equal parts by weight Polyethylene glycol and water are mixed is about 12°C for PEG 200 and about 14°C for PEG 600.
Even solid Polyethylene glycol grades have excellent solubility in water.
For example, 75 parts by weight of PEG 1000 can be dissolved at room temperature in only 25 parts by weight water.
Although the solubility in water falls slightly with increasing molar mass, it does not fall below 50% even in the case of PEG 35000.
The dissolving process can be greatly accelerated by heating about the melting point.
PEGs exhibit nonionic behaviour in aqueous solution.
They are not sensitive to electrolytes and are therefore also compatible with hard water.
WATER CONTENT:
When our Polyethylene glycols are despatched, the water content is not mote than 0.5 %.
Some pharmacopoeias permit a maximum water content of 2%.
If necessary, the water content can be reduced to 0.1% in drying oven at 105°C; with fresh or well regenerated molecular sieves (pore size 3-4 Å) it can be reduced to 0.05%.
NON-VOLATILITY AND THERMAL STABILITY of Polyethylene glycols:
Polyethylene glycols are non-volatile, a factor of consider able importance in connection with their use as plasticizers and humectants.
If a certain weight loss is established despite the non-volatility of Polyethylene glycols when maintained at a constant temperature of 150°C and above (e.g. when used as heating bath liquids), this is due not to evaporation but to loss of volatile products of decomposition.
The breakdown products of Polyethylene glycols may vary, depending on the ingress of air; apart from water, carbon dioxide and aldehydes, simple alcohols, acids and glycol esters are formed.
Troublesome fumes from decomposition products have not been known to have an adverse effect on health.
Since the lower Polyethylene glycol grades are hygroscopic, moisture may be reabsorbed in the case of fairly long down times.
At temperatures above 100°C it is essential to add a suitable antioxidant to Polyethylene glycol.
The type an quality of antioxidant is governed by the requirements imposed on Polyethylene glycol.
Thus, not only the temperature and dwell time but also the physiological properties of the antioxidant and its solubility or insolubility in water must be taken into consideration.
Where exposure to high thermal stress is involved, up to 3% antioxidant should be added.
The following substances have proved effective as antioxidants:
1. trimethyl dihydroquinoline polymer
2. diphenylamine derivatives
3. phenothiazine
4. phenyl-alpha-naphtylamine
5. 4,4‘-methylene-bis.2,6-di-tert.-butylphenol
6. butylated hydroxyanisole (BHA)
7. methoxy phenole (hydroxyanisole)
HYGROSCOPICITY of Polyethylene glycol Grades:
The liquid Polyethylene glycol grades are hygroscopic, although not to the same extent as diethylene glycol or glycerol for example.
The ability to absorb water decreases with increasing molar mass.
A rule of thumb is:
With a relative humidity of about 50% PEG 200 has about ¾ of the hygroscopicity of glycerol.
PEG 400 has about half, PEG 600 a third and PEG 1000 only a quarter.
PEG 2000 and higher grades are no longer hygroscopic.
Polyethylene glycols take moisture from the air until an equilibrium is reached.
By plotting the water content of the substance in the equilibrium state as a function of the relative humidity, absorption isotherm is obtained.
The moisture absorption of lower glycols such as monoethylene glycol, diethylene glycol or 1,2-Propylene glycol corresponds roughly to that of glycerol.
An adaptable moderate hygroscopicity may be advantageous for a conditioning agent because products treated with it are less sensitive to climatic changes and have better storage stability.
SOLUBILITY PROPERTIES of Polyethylene glycols:
The excellent solubility characteristics of Polyethylene glycols are of great importance in relation to their applications.
Two advantages are especially significant:
Firstly, the ability of Polyethylene glycols to dissolve many substances and, secondly, their good solubility in numerous solvents.
In the preparation of aqueous solutions Polyethylene glycols sometimes act as specific solubilizers.
The dissolving power and the solubility of Polyethylene glycols decrease as the molar mass increases.
Both properties are improved by heating.
Here is a list of solvents in which the liquid Polyethylene glycols are very readily miscible and in which the solid PEGs dissolve:
-Alcohols e.g. ethanol, isopropanol, benzyl alcohol
-Esters e.g. methyl acetate, butyl acetate
-Glycol ethers e.g. methyl glycol, butyl glycol and their acetates
-Ketones e.g. acetone, cyclohexanone
-Chlorinated e.g. ethylene chloride, hydrocarbons chloroform
-Benzene e.g. benzene, xylene hydrocarbons
COMPATIBILITY OF POLYETHYLENE GLYCOLS:
Polyethylene glycols have good compatibility with cetyl alcohol, glycerol, stearic acid, polyvinyl pyrrolidone, casein, vegetable albumin, dextrin, starch, chlorinated starch and various resins, e.g. colophony.
Some ethereal oils are absorbed extremely well by liquid and molten Polyethylene glycols.
SUBSTANCES SOLUBLE IN Polyethylene glycols:
Substances that dissolve at room temperature in PEG 400 are soluble to roughly the same extent in molten PEG 4000 (60-70°C).
The following values indicate the approximate percentage of PEG 4000 in the solutions saturated at room temperature:
Aniline 30 % (m/m)
Benzene 10
Carbon tetrachloride 10
Chloroform 47
1,4-Dioxane 10
Ethanol 60% 50
Ethylene chloride 46
Formamide 30
Methanol 20
Methylene chloride 53
Pyridine 40
Trichlorethylene 25
Water 55
White spirit i.
Xylenol 50
The solubility of Polyethylene glycols increases sharply with rising temperature.
This means that a Polyethylene glycol that is insoluble at room temperature can be brought into solution by moderate heating
It is worth noting that solid Polyethylene glycols are completely insoluble in liquid PEGs at room temperature.
PHYSICAL FORMS OF Polyethylene glycols:
All solid Polyethylene glycols (1500-35000) are available as flakes with sizes of about 0.3 to 2 cm.
Polyethylene glycol grades 3000 to 20000 are available in powder form (P), the grades 4000 to 8000 also as fine powders (PF) and 3350 to 4000 as spray dried powders (PS).
Solid Polyethylene glycols are used in powder form wherever it is necessary for them to be intimately drymixed with component of a different kind, for example in tablet manufacture, or in dry granulation.
ANIMAL TOXICITY:
-Acute oral toxicity Macrogols (polyethylene glycols) are considered as practically non-toxic compounds.
Acute oral toxicity, expressed as the median lethal dose (LD50), is reported to be 30.000 to 50.000 mg/kg body weight in various animal species.
Higher molecular weight PEGs exhibit even greater LD50 -values above 50.000 mg/kg body weight.
-Chronic oral toxicity:
Smyth et al. summarized the extensive feeding studies they conducted with Macrogols.
For example polyethylene glycols having average molecular weights of 400, 1500 and 4000 caused no adverse effect in dogs when fed two percent in their diet for one year.
Several percent of Macrogols can be tolerated in the diet of rats without appreciable effects, indicated that they are exceptionally low in chronic oral toxicity.
-Eye irritation:
Macrogols do not cause appreciable irritation to the eyes of rabbits .
Due to their ether characteristics, Polyethylene glycols are capable of forming complexes which are difficult to dissolve.
Precipitation with silicotungstic acid in the presence of barium chloride is used to determine Polyethylene glycols gravimetrically.
Polyethylene glycols can also be determined quantitatively by precipitation with sodium tetraphenyl borat.
The modified Dragendorff reagent can be employed for the detection of Polyethylene glycols and for sedimetric determination.
Phosphomolybdic acid is used for colorimetric determination.
None of the above-mentioned quantitative methods of precipitation is very easy to carry out, particularly as the molar mass of Polyethylene glycol in question has to be know in order to be able to evaluate the results.
To determine PEGs in the molar mass range from 300 to 1000 colorimetrically, complexes of Polyethylene glycols with ammonium cobalt thiocyanate are suitable.
Applications of Polyethylene glycols:
PEGS AS EXCIPIENTS:
-Liquids:
The very good solvent power leads to a broad use of low molecular weight Polyethylene glycols 200 to 400 in liquid preparations such as drops, parenterals or fillings for gelatin capsules.
Polyethylene glycol does not soften gelatin.
The liquid Polyethylene glycols have a slightly bitter taste, which can easily be adjusted by suitable additives (sweeteners).
Solid Polyethylene glycol grades show a neutral taste.
-Ointment basics:
It is very interesting that solid Polyethylene glycols are not soluble in liquid polyethylene glycols.
Blending pasty or solid Polyethylene glycols together with liquid PEGs will lead to a white, pasty ointment with good solubility in water, good dissolving properties and suitable for many active substances.
Polyethylene glycol bases can also be combined with other base, e.g. cetyl alcohol, cetyl stearyl alcohol, stearic acid, 1,2 propylene glycol, glycerol, glycerol monostearate and PEG sorbitan monooleate.
Polyethylene glycols are not compatible, however, with paraffin way, petroleum jelly, oleyl oleates and hydrogenated peanut oil.
Examples of Polyethylene glycol-compatible pharmaceuticals (47 – 52) are:
- Ammonium bituminosulphonicum
- Benzalkonium chloride
- Bismuth gallate, basic
- Camphor
- Chloramphenicol
- Diphenhydramine
- Hydrocortisone acetate
- Iodochlorohydroxyquinoline
- Nitrofurantoin
- Nitrofurazone
- Phenoxyethyl alcohol
- Polymyxin B
- Prophenpyridamine
- Sulphanilamide
- Sulphathiazole
- Sulphisomidine
- Trypafl avin
- Undecylenic acid and its salts
-Suppositories:
Solid polyglycols are preferred bases for suppository masses.
Numerous actives can be dissolved in Polyethylene glycols and have then a good bioavailability .
The dissipation of the active takes place not only by melting within the body but also by dissolving the body fluids.
During the manufacturing they show easy release from the mold, high stability and no refrigeration is required during storage.
The desired solidity can be adjusted by choosing the molecular weight and suitable ratios.
For example 25% PEG 1000 and 75% PEG 1500 S give very soft masses, whereas 25 % PEG 4000 S and 75% PEG 6000 S will give more solid products.
-Tablets:
The manufacture of tablets requires numerous excipients with different functions, several of them covered by Polyethylene glycols.
Polyethylene glycols may be carriers, solubilizers and absorption improvers for active substances, usually processed in the form of a melt (melt granulation), of course restricted to cases where the active substances withstand heating to about 70°C.
They also act as lubricants and binders during the tablet processing.
The relatively law melting point favour a sintering or compression technique.
At the same time Polyethylene glycol has a plasticizing effect which facilitates the shaping of the tablet mass in the compression process and may counteract capping.
Solid Polyethylene glycols are also frequently used in tablet coatings.
The flexibility of sugar-coated tablets is increased by Polyethylene glycols and since polyethylene glycol acts as a anticaking agent, the cores are prevented from sticking together.
With usually used fi lm formers in sugar-free coatings Polyethylene glycol acts as softener
PEGS AS ACTIVES:
-Ophthalmic demulcents:
Polyethylene glycol 300 and 400 are listed as active ingredients in ophthalmic demulcents in amounts of 0.2 to 1%.
Polyethylene glycols are treated as one class of compounds, also reflected by the use of one single CAS number for the whole class of polyethylene glycols, it is likely that higher molecular weight PEGs show similar properties for this application.
Thus polyethylene glycol 6000 is also listed as an ophthalmic demulcent active ingredient.
-Laxatives
Since polyethylene glycol is both highly water soluble and not absorbed by humans (60), it is superior to solutions of other difficult to absorb materials with an osmotic mode of action, such as e.g. mannitol.
Polyethylene glycols cause fewer side effects such as nausea or gas formation.
Since up to now there is no review article available dealing with the osmotic activity of Polyethylene glycols, only some examples from the literature are cited in the appendix
The USP/NF describes a blend in the monograph “PEG 3350 and Electrolytes for Oral Solution” which contains a detailed description of all potential individual salt components to be used in addition to the polyglycol with a mean molecular weight of 3350.
The existence of this monograph explains why the mean molecular weight of 3350 is used so frequently in laxative preparations, although Polyethylene glycols with other molecular weights would have an essentially equivalent effect.
The confusing nomenclatures (see page 7) also contribute to the use of the type 3350, since this type is registered in Japan (under the name “4000”).
Remarks on the Manufacture of Laxatives on an Industrial Scale:
During the manufacture of laxative blends, the homogenous distribution of all ingredients is very important.
A key criteria is the particle size distribution of all the ingredients, which are normally used in powder form.
The more similar the particle size distributions of the different powders, the easier it will be to produce a homogenous blend.
On the other hand the powder must not be too fine, since the generation of dust complicates the final filling of the material.
Also the moisture content of the hygroscopic polyethylene glycol plays an important role, since “moist” polyglycols lead to sticking and lumping in the filling equipment.
-Organ preservations:
A very specifi c and interesting application is the use of linear high molecular weight polyethylene glycol (20000 daltons) in compositions that exhibit antiapoptotic activity that can be used therefore to protect, preserve or restore cell, tissue or organ function.
In this application the polyethylene glycol must be seen as the active ingredient.
The full explanation, why PEG shows the antiapoptotic activity and why longer chains are more efficient than short ones is missing yet.
Collins (68) suggests that the higher molecular weight PEG has a direct tolerogenic action on donor antigen in the transplanted organ.
He assumes that some sort of attachment of PEG to transplantation antigens must have occurred, without chemical combination, but this is not proved.
An earlier explanation from Daniel (69) is that an essential component of the medium is a non toxic solute which does not cross the cell membrane a low temperatures and could therefore counterbalance the osmotic effect of the intracellular proteins.
PEGS AS REACTION COMPOUNDS:
OF DRUG DELIVERY SYSTEMS:
With the who OH-groups at the ends of the polyethylene glycol molecules, all reactions typical for alcohols are possible, such as esterification, carbonates and carbamates formation.
To avoid chain-building reactions Methyl-ether-capped Polyethylene glycols, so called Methylpolyethylene glycols, are available.
INCOMPATIBILITY:
Polyethylene glycols are unsuitable as based for bacitraicine and penicillin G an W (compete inactivatio (77)); for sulphanilthiocarbamide (evaluation of hydrogen sulphide); acetylsalicylic acid (release of salicylic acid due to transesterification; and also where discoloration is undesirable
Substances capable of forming precipitates with Polyethylene glycols in aqueous solution at particular concentrations are, for instance, phenol, cresols, resorcinol, salicylic acid, ß-naphthol, tannin and potassium iodide
COSMETIC INDUSTRY:
Polyethylene glycols can be used in the following cosmetic preparations:
-Creams, lotions, facial lotions:
In creams, as in all preparations that tend to dry out, Polyethylene glycols have a moisture- stabilizing effect and also a conditioning effect on the skin treated.
After application, they leave a pleasant feel on the skin similar to the natural replacement of oils without producing any sensation of stickiness.
In lotions and face lotions Polyethylene glycol acts as a cleansing agent.
In after-shave lotions Polyethylene glycol has the additional function of a non-greasy lubricant and perfume stabilizer.
The most suitable type is PEG-8 (POLYETHYLENE GLYCOL 400).
-Deodorant, perfume and insect-repellent sticks:
Polyethylene glycols are ideal carriers for sodium stearate and sodium aluminium hydroxylactate.
Unlike ethanol or isopropanol, they are not volatile and thus permit reliable control of deodorant, perfume and insect-repellent sticks .
The most suitable grades are the liquid types PEG-4 to PEG-12 (POLYETHYLENE GLYCOL 200 USP to POLYETHYLENE GLYCOL 600).
PEGs prove to be outstanding solubilizers for hexachlorophene, dimethyl phthalate, azulene, aluminium hydroxychloride, etc.
-Lipsticks:
Polyethylene glycols can be used in lipsticks as solubilizers for tetrabromofl uorescein and its derivatives.
The solubility in PEG-8 (POLYETHYLENE GLYCOL 400) is about 10%. Higher additions of Polyethylene glycol should be avoided because of their good solubility in water, since dyes then tend to “bleed”.
-Toothpastes:
Since Polyethylene glycols are non-toxic and not-irritant, they meet the requirements for incorporation in toothpastes, where their main function is to improve the consistency and storage stability.
Thus glycerol and sorbitol can be replaced by Polyethylene glycols in toothpaste formulations.
With increasing molar mass the slightly bitter taste of Polyethylene glycols, which can be easily counteracted by sweeteners, is less pronounced.
PEG-4 to PEG-40 (POLYETHYLENE GLYCOL 200 USP to POLYETHYLENE GLYCOL 2000 S) are recommended.
Polyethylene glycol has been proven to be highly successful in the production of transparent toothpastes.
By using Polyethylene glycol, the refractive index of the mixture, which usually contains a large amount of silicic acid, can be adjusted to achieve good transparency.
-Soaps, hand-cleanings pastes and detergent sticks:
PEG 450 (POLYETHYLENE GLYCOL 20000 S) is particularly suitable for use as a milling aid in toilet soap manufacture.
Not only does it facilitate mechanical plasticization, it also improves the sharpness of the moulded bar contours.
Polyethylene glycol stabilizes the perfume and later prevents the soap from frying out and cracking.
Initial lathering is accelerated without affecting the foaming characteristics.
Polyethylene glycols prevent handcleansing pastes form drying out and leave a pleasant feel on the skin once they have dried.
Very soft smooth shaving creams can also be produced with Polyethylene glycols.
Soap-free blocks (detergent blocks) can be moulded or pressed when Polyethylene glycols are incorporated.
In this application PEG-32 to PEG-450 in the relative molar mass range of 1500 to 20000 are suitable as readily water-soluble carriers.
The strength and solubility in water can be adjusted by the addition of a small amount of cetyl alcohol.
-Hair care products facial masks and depilatories Polyethylene glycols have proved successful as additives for improving the consistency of non-greasy haircare products, which can be washed off after use with clear water, a requirement that is met by PEGs, especially PEG-8 (POLYETHYLENE GLYCOL 400).
-Hair styling:
The efficacy of aerosol hair spray and styling products is based on synthetic resins such as cellulose derivatives, polyvinyl alcohol and acetate, polyvinyl pyrrolidone, etc.
As a plasticizer and antistatic agent, PEG-8 counteracts the tendency of these substances to dry to a brittle film.
-Bath oils and foam baths:
In formulations of bath oils, etc. PEG-4 to PEG-40 assist the solubilizing action of the active substances for perfume oils.
In addition, consistency and skin compatibility are improved.
-Denture cleaners:
Bath cubes, effervescent tablets Polyethylene glycols are excellent binder when bath salts, denture cleaners etc. are pressed into tablets.
By choosing the appropriate grade, e.g. PEG-75 to PEG-450 (POLYETHYLENE GLYCOL 3350 P to POLYETHYLENE GLYCOL 20000 P), and by incorporating suitable amounts, the dissolving rate can be controlled as required.
FOOD INDUSTRY:
In the USA Polyethylene glycols 200 to 9500 are approved, in accordance with the FDA, as auxiliaries and additives in the manufacture of consumer articles that come into contact with food.
In certain cases they are also approved as components of the foodstuff itself, e.g. as binders and plasticizers for foods in tablet form, as excipients for tablet coatings, as carriers for aromatic substances, calorie-free sweeteners and as defoamers.
Safety and Handling of Polyethylene glycol:
Polyethylene glycols are non-toxic and physiologically safe so no special safety precautions need to be taken when handling them.
For many applications, particularly in pharmaceuticals, cosmetics and foodstuffs packaging, the physiological safety of Polyethylene glycols is important.
When administered orally and cutaneou sly they are to be rated as non-toxic.
The vapour pressure of Polyethylene glycols is so low that inhalation of relevant amounts is impossible.
Because of their good physiological tolerability Polyethylene glycols were fi rst included in the US pharmacopoeia already in 1950.
Since then they have been listed in numerous pharma copoeias.
The tolerability of Polyethylene glycols in animals improves as the degree of polymerization rises.
Polyethylene glycols have no toxic or irritant effect on the skin.
Because of low toxicity it was not possible to establish an exact LD50 resulting from skin penetration.
The CAS number for all Polyethylene glycols is 25322-68-3.
RECOMMENDED CONDITIONS:
Polyethylene glycols are stable for 2 years when stored in the original sealed containers in a cool, dry place.
Furthermore the containers should not be exposed to direct sun light.
Ambient temperatures for long term storage are preferably between 10°C and 25°C and between 0°C and 30°C as maximum.
Storage at higher temperatures is possible only for a short time and should be kept below the solidifi cation point of the products (for POLYETHYLENE GLYCOL 1000 to 35000).
It is essential to ensure storage in a dry place because liquid Polyethylene glycols are hygroscopic and the solid grades immediately in water.
Each time the containers are opened, they should be resealed to make them airtight.
Even with sealed laboratory containers it is impossible to prevent atmospheric oxygen and moisture acting on Polyethylene glycol owing to frequent opening (92).
We therefore recommend that laboratory samples should also not be stored longer than 2 years.
The most suitable material for storage tanks is stainless steel, pure aluminium, rubber-or polyethylene-lined containers and storage tanks made from glass-fi bre-reinforced polyester (GRP).
The tank should be ventilated by means of a silica gel dryer.
Conventional steel tanks are of limited suitability because after prolonged storage the product may become discoloured owing to traces of iron.
Liquid PEG should not be stored in internally lacquered containers because normal coatings are dissolved (epoxy and stoving enamels are resistant, however).
Storage of Polyethylene glycol:
Polyethylene glycols 600 to 1000 solidify when stored in a cool place and must be melted before use.
This is best carried out in heating chambers, but the outside temperature should not exceed about 60°C.
This must also be ensured when electrical drum heaters are used.
Electrical immersion heaters are no suitable for melting owing to the high thermal stress occurring.
The recommended method of storing Polyethylene glycols 800 to 8000 in the molten state is in stainless steel or aluminium containers fitted with an external, heating coll.
The storage temperature of Polyethylene glycol should not exceed 70°C, and it is advisable to thoroughly mix the contents of the storage container with a dry nitrogen stream or a circulating pump.
AVAILABLE TYPES of Polyethylene glycol:
POLYETHYLENE GLYCOL 200 USP
POLYETHYLENE GLYCOL 300
POLYETHYLENE GLYCOL 400
POLYETHYLENE GLYCOL 600
POLYETHYLENE GLYCOL 800
POLYETHYLENE GLYCOL 1000
POLYETHYLENE GLYCOL 1500 S / FL
POLYETHYLENE GLYCOL 2000 S
POLYETHYLENE GLYCOL 3000 S / P
POLYETHYLENE GLYCOL 3350 S / P / PS
POLYETHYLENE GLYCOL 4000 S / P / PF / PS
POLYETHYLENE GLYCOL 6000 S / P / PF
POLYETHYLENE GLYCOL 8000 S / P / PF
POLYETHYLENE GLYCOL 10000 S / P
POLYETHYLENE GLYCOL 12000 S / P
POLYETHYLENE GLYCOL 20000 S / P
POLYETHYLENE GLYCOL 35000 S
Other names:.
Carbowax, GoLYTELY, GlycoLax, Fortrans, TriLyte, Colyte, Halflytely, macrogol, MiraLAX, MoviPrep
IUPAC names:
poly(oxyethylene)
poly(ethylene oxide)
CAS names:
Poly(oxy-1,2-ethanediyl), .alpha.-hydro-.omega.-hydroxy-
IUPAC names
3,6,9,12,15,18,21,24,27,30,33,36,39-tridecaoxahentetracontane-1,41-diol
a,w-Hydroxypoly(ethylene oxide)
alpha-Hydro-omega-hydroxypoly(oxy-1,2-ethanediyl)
ethane-1,2-diol
Ethane-1,2-diol, ethoxylated
Polietilenoglicol
Poly(ethylene glycol)
Poly(ethylene glycol), flake, 600
Poly(oxy-1,2-ethanediyl) , .alpha.-hydro-.omega.-hydroxy-
Poly(oxy-1,2-ethanediyl), .alpha.-hydro-.omega.-hydroxy-
Poly(oxy-1,2-ethanediyl), .alpha.-hydro-.omega.-hydroxy- (90,000 mol EO average molar ratio)
Poly(oxy-1,2-ethanediyl), .alpha.-hydro-.omega.-hydroxy-Ethane-1,2-diol, ethoxylated
Poly(oxy-1,2-ethanediyl), a-hydro-w-hydroxy-
Poly(oxy-1,2-ethanediyl), alpha-hydro-omega-hydroxy-
Poly(oxy-1,2-ethanediyl), α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
Poly(oxy-1,2-ethanediyl),-hydro-hydroxy- Ethane-1,2-diol,
Poly(oxy-1,2-ethanediyl),.alpha.-hydro-.omega.-hydroxy
Poly(oxy-1,2-ethanediyl),.alpha.-hydro-.omega.-hydroxy;
Poly(oxy-1,2-ethanediyl),?-hydro-?-hydroxy- Ethane-1,2-diol, ethoxylated
Poly(oxy-1,2-ethanediyl),??-hydro-??-hydroxy- Ethane-1,2-diol, ethoxylated
Poly(oxy-1,2-ethanediyl),a-hydro-?-hydroxy- Ethane-1,2-diol, ethoxylated
Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy
Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol
Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylate
Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy- Ethane-1,2-diol, ethoxylated
Poly(oxy-1,2-ethanediyl),α-hydro-ω-hydroxy-Ethane-1,2-diol, ethoxylated
Poly(oxyethylene)
poly(oxyethylene)
poly(oxyethylene) {structure-based}
poly(oxyethylene) {structure-based}, poly(ethylene oxide) {source-based}
POLYETHYLENE GLYCOL
Polyethylene Glycol
Polyethylene glycol
polyethylene glycol
Polyethylene glycol
Polyethylene Glycol 1000
Polyethylene glycol 3,350
Polyethylene glycol 400
Polyethylene Glycol 400
Polyethyleneglycol
polyethyleneglycol
polyethylenglycol
Polyethylenglykol
Polyethylenglykole (PEG)
Polymer aus Ethylenglycol
α-Hydro-ω-hydroxypoly(oxy-1,2-ethanediyl)
α-hydroxy-ω-hydroxy-poly(oxy-1,2-ethanediyl)