PEG 8000
PEG 8000
Composition: Polyethylene glycol
H(OCH2CH2)nOH
n = about 181
CAS-No.: 25322-68-3
INCI-designation: PEG-180
Chemical name: polyethylene glycol 8000
Polyglykol 8000
CAS Number: 25322-68-3
General description
Polyethylene glycol 8000 (PEG 8000) is a hydrophilic polymer.
PEG 8000 can be easily synthesized by the anionic ring opening polymerization of ethylene oxide, into a range molecular weights and variety of end groups.
When crosslinked into networks PEG can have high water content, forming “hydrogels”.
PEG 8000 is a suitable material for biological applications because it does not trigger an immune response
PEG 8000 is a water-soluble linear polymer formed by the addition reaction of ethylene oxide with a molecular weight of 7000 to 9000.
PEG 8000 is high molecular weight Polyethylene Glycol that provides enhanced solvency, lubricity, hygroscopicity and other important functional properties in a wide range of formulations.
INCI Name: PEG-180
Uses:
Fragrance carrier
Binder and plasticizer for green-body formation in ceramics
Wetting for after wash automotive sprays
Household cleaners
Dye carrier
Lubricants
Mining
Mold release agent
Plasticizer
Wood treating
PEG 8000 (POLYETHYLENE GLYCOL 8000)
PEG 8000 (CAS No. 25322-68-3) is a polyethylene glycol having white to off white color and available in solid flakes or powder form.
PEG 8000 used as a base in the formulation of soap sticks. PEG 8000 has low glycol content and higher crystalinity.
Its high molecular weight mainly prompts its use in pharmaceutical formulations as solvent for oral, topical and parenteral preparations.
The high molecular weight PEG 8000 is soluble in water and organic solvents such as alcohols.
It can blend with other PEG molecular weights to achieve the desired viscosity properties.
PEG 8000 is quite stable and does not support microbial growth, even in aqueous solutions.
PEG 8000 is a high molecular polyethylene glycol (macrogol) mainly used as solvent for oral, topical and parenteral preparations.
Polyethylene glycol 8000 (PEG 8000) has been used in pharmaceutical applications for over 50 years, giving this inactive ingredient a wide acceptance.
PEG 8000 is a high molecular polyethylene glycol (macrogol) mainly used as solvent for oral, topical and parenteral preparations.
The high molecular weight PEG 8000 is soluble in water and organic solvents such as alcohols.
It can be blended with other PEG molecular weights to achieve the desired properties, i.e. viscosity.
PEG 8000 will not become rancid and will not support microbial growth, even in aqueous solutions.
PEG 8000 offers water solubility, nonvolatility, inertness and lubricity to the formulations
Polyethylene Glycol 8000 is an ideal choice for a variety of household product applications.
Polyethylene Glycol 8000 serves as an excellent laundry aid for powdered detergents in need of anti-caking properties, and acts as a carrier for starch.
PEG 8000’s binding properties make this PEG ideal for detergent cake applications and toilet bowl cleaners with added dissolution control to deliver the convenient and high-performing solutions consumers desire.
In ceramics applications, Polyethylene Glycol 8000 delivers the extra edge products need as a plasticizer, binder, and carrier with easy and smooth distribution, good lubricity for mold and die release, improved green-strength and easy burn-off without residue.
Polyethylene Glycols (PEGs), a family of water soluble linear polymers, are among the most versatile chemical ingredients available to formulators and manufacturers.
They are available in a wide range of viscosities, weights from 200 to 35000 and melting points for optimal formulation flexibility in applications including ceramics, lubricants, soaps and detergents, and toilet bowl cleaners.
By choosing a suitable product grade, you can achieve the desired balance of water solubility, hygroscopicity, vapor pressure, melting or freezing range, and viscosity.
Product properties*)
Polyglykol 8000 is a white waxy solid at room temperature.
Polyglykol 8000 is a flaked type,
Its two hydroxy end groups as well as its ether groups mainly control the physical and chemical properties of Polyglykol 8000.
Therefore Polyglykol 8000 is soluble in water and polar organic solvents like aceton or methanol.
Polyglykol 8000 is insoluble in pure hydrocarbons.
Polyglykol 8000 displays typical chemical reactions of alcohols/diols.
The solidification point, of Polyglykol 8000 is about 58°C
Kollisolv PEG 8000
Chemical Name: Poly(ethylene glycol)
CAS-No: 25322-68-3
Pluriol E 8000
Lutrol E 8000
PEG 8000 White or almost white solid with a waxy or paraffin-like appearance.
PEG 8000 Very soluble in water and in methylene chloride, very slightly soluble in alcohol, practically insoluble in fatty oils and mineral oils
USP/NF: Polyethylene glycol 8000
Storage
When stored in a cold, dry place in a closed container Polyglykol 8000 can be kept for at least two years.
Applications
Based on their physical and chemical characteristics – polyethylene glycol 8000 is used for a wide variety of applications.
Fields of application:
– Reactive diol/polyether component in polyester or polyurethene resins
– Component of auxiliaries for leather and textile processing
– Cosmetic / pharmaceutical formulations (e.g. humectant or plasticiser for creams, tablets, tooth paste)
– Lubricant and mould release agent for rubber, plastic and elastomer processing
– Plasticizer and binder for ceramic and concrete manufacturing
– Component of lubricant formulations
– Water soluble, lubricating component in metalworking fluids
– Humectant for paper, wood and cellulose films
– Solvent and humectant for dyes and inks
– Modifier for production of regenerated viscose
– Humectant and plasticizer for adhesives
Application of PEG 8000 includes washing powders and tabs, dissolving aids, tabletting and granulation auxiliaries, binding agents, toilet blocks.
Product data*)
water content (DIN 51777) % m/m max. 0.5
max. 0.1 (8000 FL)
colour index [APHA] (EN 1557) (25 % in water) max. 30
pH (5 % w/w in water) (DIN EN 1262) 5 – 7
hydroxyl number (DIN 53240) mg KOH/g 12 – 16
molecular weight g/mol 7300 – 9000
solidification point (EP III) °C 55 – 60
viscosity at 20°C (50 % w/w in water) (DIN 51562) mPas 290 – 450
flash point (DIN 51376) °C 255
ignition temperature (DIN 51794) °C >320
ethylene oxide ppm max. 1
dioxane ppm max
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.
X-ray structural analysis has shown that PEG chain may possess two different types of microstructure.
The shorter chains, with a degree of polymerization not exceeding 10, are said to have a zigzag structure, while longer chains form a so-called meandering structure.
The oxygen forms ether bridges at regular intervals in both types of chain which are responsible for many of the properties of PEGs (3-5).
The microstructure of PEG molecular chains is important in relation to the behaviour of PEGs towards various solvents and also to the formation of addition compounds which link with the “residual valencies” of the ether oxygen atoms.
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.
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.
Polyglykols up to a molecular weight of 35000 are commercially available.
The hardness of Polyglykols 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 PEGs is their solubility in water, making them ideally suited for use in countless different applications.
Liquid PEGs up to PEG 600 are miscible with water in any ratio.
But even solid PEG 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 PEGs are nonionic substances.
PEGs are quite soluble in hard water or in other aqueous solutions of various salts.
Some physical and chemical properties are described in more detail in the following chapters.
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.
SOLUBILITY IN WATER
When liquid PEGs 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 PEG and water are mixed is about 12°C for PEG 200 and about 14°C for PEG 600.
Even solid PEG 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.
NON-VOLATILITY AND THERMAL STABILITY
PEGs 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 PEGs 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 PEGs 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 PEG 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 PEG.
The type an quality of antioxidant is governed by the requirements imposed on PEG.
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)
As the following fi gure shows, oxidative decomposition can be slowed down considerably by the addition of antioxidants even at high temperatures (200°C).
The bath was stabilized with 3% of one of the inhibitors numbered 1 to 4 in turn.
No major differences were observed between the individual substances.
The pure thermal egradation without presence of oxygen can hardly be infl uenced with antioxidants.
Curve 1 applies to the following stabilizers (3% addition):
– trimethyl dihydroquinoline polymer
– diphenylamine-styrene adduct
– phenothiazine
– phenyl-alpha-naphtylamine
The phenolic stabilizers numbered 5-7 in the list are effective only at lower temperatures
– up to about 150°C – but have two advantages:they cause less discoloration and some of them are water-soluble.
The ingress of air should be excluded if possible or the bath should be blanketed with an inert gas atmos phere (nitrogen, carbon dioxide, etc.).
This applies particularly to temperatures between 200 and about 220°C.
Hot PEGs attack iron and steel only slightly, but as a precaution when liquid PEGs are used, a certain margin of alkalinity should be created by the addition of about 0.3% hydrated borax or triethanolamine.
Other materials should be tested to establish their resistance to corrosion by PEGs.
HYGROSCOPICITY
The liquid PEG 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.
PEGs 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-ropylene 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
The excellent solubility characteristics of PEGs are of great importance in relation to their applications.
Two advantages are especially significant:
Firstly, the ability of PEGs to dissolve many substances and, secondly, their good solubility in numerous solvents.
In the preparation of aqueous solutions PEGs sometimes act as specifi c solubilizers.
The dissolving power and the solubility of PEGs decrease as the molar mass increases.
Both properties are improved by heating.
Here is a list of solvents in which the liquid PEGs 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
PEGs 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 PEGs.
SOLUBLE IN PEGs
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:
% (m/m)
Aniline 30
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 PEGs increases sharply with rising temperature, as the following example shows:
PEG 20000 is soluble in pure ethanol as follows
at 20°C 0.1%
at 32°C 1%
at 34°C about 20%
This means that a PEG that is insoluble at room temperature can be brought into solution by moderate heating.
It is worth noting that solid PEGs are completely insoluble in liquid PEGs at room temperature.
SOLUBILITY OF VARIOUS SUBSTANCES IN PEG 400 AT ROOM TEMPERATURE
A
Acetanilide 16%
Acetic anhydride ∞
Acetone ∞
Acrylic acid ∞
Acrylonitrile ∞
Allyl alcohol ∞
Ammonia (25%) ∞
Amyl acetate ∞
Amyl alcohol ∞
Aniline ∞
Antipyrine 10%
Azulene (guaia azulene) 10%
B
Beeswax i.
Benzaldehyde ∞
Benzene ∞
Benzocaine 50%
Benzoic acid 10%
Benzyl alcohol ∞
Borax cryst. 0.3%
Bromobenzene ∞
n- Butanol ∞
Butyl acetate ∞
Butylamine ∞
Butyl diglycol ∞
Butyl glycol ∞
Butyl glycolate ∞
C
Calcium chloride • 2 H2O *20%
Camphor 10%
Carbon disulphide 10%
Carbon tetrachloride ∞
Carnauba wax i.
Casein i.
Castor oil 1%
Ceresin wax i.
Cetyl alcohol sl.c.s.
Cetyl stearyl alcohol sl.c.s.
Chloral hydrate 50%
Chloramine T 10%
Chlorobenzene ∞
Chloroform ∞
Chlorothymol 50%
Chlorparaffi n 56 and 70 ∞
Citric acid 25%
Cobalt (III) chloride • 6 H20 *50%
Coconut fatty amine 10%
Colophony 50%
Copper (III) chloride • 2 H2O ∞
Cresol 20%
Cyclohexane i.
Cyclohexanol ∞
Cyclohexanone ∞
D
Diacetone alcohol ∞
Dibutyl phthalate ∞
ß,ß-Dichloroethyl ether ∞
Di-(2-ethylhexyl) phthalate i.
Diethanolamine ∞
Diethylene glycol ∞
Diethylene glycol dimethyl ether ∞
Diisopropyl adipate ∞
Dimethyl acetamide ∞
Dimethyl formamide ∞
Dimethyl phthalate ∞
Dimethyl sulphoxide ∞
Dioctyl phthalate i.
Dioxane ∞
Diphenyl ether ∞
Dipropylene glycol ∞
Dodecyl alcohol ∞
E
Eosinic acid 10%
Ephedrine (1/2 H2O) 20%
Ester waxes i.
Ethanol ∞
Ethyl acetate ∞
Ethylbenzene ∞
Ethylene diglycol ∞
Ethylene glycol ∞
Ethylene glycol acetate ∞
2-Ethylhexenol ∞
Ethyl urethane 50%
Ethylene chloride ∞
Eucalyptus oil 10%
F
Formamide ∞
Furfural ∞
G
Gelatin i.
Glacial acetic acid ∞
Glycerol ∞
Glycerol monoestearate sl.s.c.
Glycerol triacetate ∞
Glycol ∞
Gum arabic i.
H
Hexachlorophene 45%
Hydrochloric acid, 37% ∞
I
Iodine 20%
Iron (III) chloride • 6 H2O *50%
Isobutanol ∞
Isobutyl acetate ∞
Isodecyl alcohol ∞
Isopropanol ∞
Isotridecyl alcohol ∞
L
Lactic acid (90%) ∞
Lavender oil 10%
Lead acetate 1%
Lead stearate i.
Lecithin i.
Lithium stearate i.
M
Magnesium chloride • 4 H2O *25%
Manganese (II) chloride • 4 H2O *40%
Menthol 10%
Mercury (II) acetate *10%
Methanol ∞
Methoxybutyl acetate ∞
Methyl acetate ∞
Methyl diglycol ∞
Methyl ethyl ketone ∞
Methyl glycol ∞
Methyl glycol acetate ∞
Methyl methacrylate ∞
Methyl salicylate ∞
Methylene chloride ∞
Mineral oils i.
Morpholine ∞
N
Naphthalene 10%
b-Naphtanol 40%
Nitrobenzene ∞
Nitromethane ∞
O
Octyl alcohol ∞
Oleic acid ∞
P
Paraffi n oil i.
Paraldehyde 50%
PEG laurate ∞
PEG sorbitan oleate sl.s.c.
Perchloroethylene 43%
Petroleum jelly i.
Phenacetin 10%
Phenol 50%
Phenol (90%) ∞
Phenothiazine 15%
Phenyl acetate ∞
Phenylmercuric acetate 10%
Phenyl salicylate 50%
Phosphoric acid (85%) ∞
Piperazine 10%
Polyethylene glycol 4000 i.
(soluble when heated)
Polypropylene glycol 400 ∞
Potassium iodide *15%
Propanol ∞
1,2.Propylene glycol ∞
Pyridine ∞
Pyrocatechol 50%
R
Resorcinol 50%
S
Saccharin 10%
Salicylaldehyde ∞
Salicylic acid 30%
Sodium chloride 0.3%
Sodium cyclamate 3%
Sodium nitrite 0.4%
Sodium sulphate i.
Sorbic acid 5%
Sorbitol sl.s.c.
Stearic acid sl.s.c
Stearylamine i.
Styrene ∞
Styrene oxide ∞
Sulphanilamide 10%
Sulphathiazole 10%
Sulphuric acid , 50% ∞
T
Tannin 50%
Terpineol ∞
Tetrahydrofuran ∞
Tetralin 55%
Thiourea 10%
Thymol 50%
Tin (II) chloride • 2H2O *55%
Trichlorobutyl alcohol 10%
1,1,1-Trichloroethane ∞
Trichloroethylene ∞
Trichloroethyl phosphate ∞
Triethanolamine ∞
Triethylene glycol ∞
U
Urea 3%
V
Vanillin 10%
Vegetable oils i.
W
White spirit i.
X
Xylene ∞
Xylenol ∞
Z
Zinc chloride • 2H2O *20%
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. (27) 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 (28).
• Skin irritation and sensitization
Although early reports by Smyth et al. (29) reported that skin sensitization was observed in guinea pigs tested with certain Macrogols, later studies show that currently produced materials are without irritation or sensitizing properties (27).
• Dermal absorption
As concluded by Smyth et al. (27) the lethal dose via dermal application of Macrogols is so large as to defy the establishment of LD50 values.
• Toxicokinetic studies / metabolism
Toxicokinetic studies on absorption, metabolism,distribution, and excretion revealed that low molecular weight Macrogols are absorbed from the rat intestine only to a very slight extent.
Higher molecular weight Macrogols are not absorbed at all.
Excretion of Macrogols is mainly via feces without any biotransformation.
HUMAN TOXICITY
• Oral toxicity
Studies with human volunteers who received oral doses of 10 grams were tolerated without any toxicological or clinical symptoms (30).
• Eye irritation
No cases of injury to human eyes have been reported nor would any be expected.
• Skin irritation and sensitization
Although early reports by Smyth et al. (29) reported that skin sensitization was observed among a few human subjects tested with certain Macrogols, later studies show that currently produced materials are without irritations or sensitizing properties (27).
• ADI-value
The acceptable daily intake (ADI-value) for polyethylene glycols in foodstuffs is defined by the World Health Organization (WHO) as a maximum of 10 mg/kg body weight (31).
PHARMACEUTICAL INDUSTRY
PEGS AS EXCIPIENTS
• Liquids
The very good solvent power leads to a broad use of low molecular weight PEGs 200 to 400 in liquid preparations such as drops, parenterals or fillings for gelatin capsules.
Polyethylene glycol does not soften gelatin.
The liquid PEGs have a slightly bitter taste,which can easily be adjusted by suitable additives (sweeteners).
Solid PEG grades show a neutral taste.
• Ointment basics
It is very interesting that solid PEGs are not soluble in liquid polyethylene glycols.
Blending pasty or solid PEGs 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.
PEG 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.
PEGs are not compatible, however, with paraffin way, petroleum jelly, oleyl oleates and hydrogenated peanut oil.
Examples of PEG-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 PEGs and have then a good bioavailability (53 – 54).
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 (55) 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 and 75% PEG 6000 will give more solid products (56).
• Tablets
The manufacture of tablets requires numerous excipients with different functions, several of them covered by PEGs.
Polyglykols 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 (57) during the tablet processing.
The relatively law melting point favour a sintering or compression technique.
At the same time PEG has a plasticizing effect which facilitates the shaping of the tablet mass in the compression process and may counteract capping.
Solid PEGs are also frequently used in tablet coatings.
The flexibility of sugar-coated tablets is increased by PEGs 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 PEG 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% (58).
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 (59).
• 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.
PEGs cause fewer side effects such as nausea or gas formation(61).
Since up to now there is no review article available dealing with the osmotic activity of PEGs, only some examples from the literature are cited here in the appendix (62 – 64).
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 (65).
The existence of this monograph explains why the mean molecular weight of 3350 is used so frequently in laxative preparations, although PEGs 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”) (66).
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 fi ne, 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 fi lling 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 (67).
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 PEGs, so called Methylpolyethylene glycols, are available.
Those MPEGs are only able to react at one end of the molecule.
The wide field of PEG conjugation to proteins and other organic molecules, e.g. anticancer drugs, would exceed the scope of this text.
Harris (70) as well as later Greenwald (71) took carefully together overviews over the so called PEGnology.
A first easy to read an shorter introduction might be for example the summaries of Bonora (72) or Veronese (73).
Concerning anticancer drugs, polyethylene glycol may work also without linked to other molecules in some cases.
In one animal test, polyglycol was found to prevent colon cancer (74), which should also prove true in humans (75, 76).
INCOMPATIBILITY
PEGs 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 (78)); and also where discoloration is undesirable (79).
Substances capable of forming precipitates with PEGs in aqueous solution at particular concentrations are, for instance, phenol, cresols, resorcinol, salicylic acid, ß-naphthol, tannin and potassium iodide
COSMETIC INDUSTRY
PEGs can be used in the following cosmetic preparations:
• Creams, lotions, facial lotions
In creams, as in all preparations that tend to dry out, PEGs 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 PEG acts as a cleansing agent.
In after-shave lotions PEG has the additional function of a non-greasy lubricant and perfume stabilizer.
The most suitable type is PEG-8 (Polyglykol 400).
• Deodorant, perfume and insect-repellent sticks
PEGs 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 (82-84).
The most suitable grades are the liquid types PEG-4 to PEG-12 (Polyglykol 200 USP to Polyglykol 600).
PEGs prove to be outstanding solubilizers for hexachlorophene, dimethyl phthalate, azulene, aluminium hydroxychloride (Locron ), etc.
• Lipsticks
PEGs can be used in lipsticks as solubilizers for tetrabromofl uorescein and its derivatives.
The solubility in PEG-8 (Polyglykol 400) is about 10%.
Higher additions of PEG should be avoided because of their good solubility in water, since dyes then tend to “bleed”.
• Toothpastes
Since PEGs are non-toxic and not-irritant, they meet the requirements for incorporation in toothpastes (85 – 88), where their main function is to improve the consistency and storage stability.
Thus glycerol and sorbitol can be replaced by PEGs in toothpaste formulations.
With increasing molar mass the slightly bitter taste of PEGs, which can be easily counteracted by sweeteners, is less pronounced.
PEG-4 to PEG-40 (Polyglykol 200 USP to Polyglykol 2000 S) are recommended.
PEG has been proven to be highly successful in the production of transparent toothpastes.
By using PEG, the refractive index of the mixture, which usually contains a large amount of silicic acid, can be adjusted to achieve good transparency. (88, 90)
• Soaps, hand-cleanings pastes and detergent sticks
PEG 450 (Polyglykol 20000) 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.
It stabilizes the perfume and later prevents the soap from frying out and cracking.
Initial lathering is accelerated without affecting the foaming characteristics.
PEGs 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 PEGs. Soap-free blocks (detergent blocks) can be moulded or pressed when PEGs 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 (90).
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 PEGs 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 (Polyglykol 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 (Aristoflex A60), polyvinyl pyrrolidone (Amine Oxide Polymers Diaformer), etc.
As a plasticizer and antistatic agent, PEG-8 counteracts the tendency of these substances to dry to a brittle film (91).
• 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 PEGs 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 (Polyglykol 3350 P to Polyglykol 20000 P), and by incorporating suitable amounts, the dissolving rate can be controlled as required.
FOOD INDUSTRY
In the USA PEGs 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.
PEGs 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 packging, the physiological safety of PEGs is important.
When administered orally and cutaneou sly they are to be rated as non-toxic.
The vapour pressure of PEGs is so low that inha lation of relevant amounts is impossible.
Because of their good physiological tolerability PEGs were first included in the US pharmacopoeia already in 1950.
Since then they have been listed in numerous pharma copoeias.
The tolerability of PEGs in animals improves as the degree of polymerization rises.
PEGs 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.
ECOLOGICAL DATA
The behaviour of PEGs in effluent is a matter of crucial importance, e.g. in their industrial use in the textile sector and in metal processing.
The rate of biodegradation of PEGs decreases with increosing molar mass.
PEGs up to molar mass 1500 are regarded as readily biodegrad able (Zahn-Wellens test).
It must, however, be borne in mind that the activated sludge requires a certain time to adapt.
In some cases the degradation of high molar mass PEGs was also observed.
The microbiological degrada tion of other substances is not inhibited by the presence of PEGs.
The toxic inhibition limit for bacteria in the fermentation tube test is 5000 mg/l.
Investigations within our own labs have shown that even in concentrations of 10000 mg/kg (1%) polyethylene glycols have no adverse effect on fish (crucian carp).
Polyethylene glycols in concentration up to 10000 mg/l exhibit no harmful effect of any kind towards daphnia and protozoa.
The German water hazard class is WGK 1.
WASTE DISPOSAL
Any PEGs to be disposed of waste can be taken, in accordance with the local regulations,to a special waste incineration plant.
None of PEGs, in concentrations up to 10,000 mg/l water, demonstrates an acute harmful effect on fish or bacteria.
PEGs with molar masses of 200 to 1500 have good biodegradability.
It is therefore possible to take them to a biological sewage treatment plant after consulting the operator provided the water and waste regulations permit.
RECOMMENDED CONDITIONS
PEGs 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 Polyglykol 1000 to 35000).
It is essential to ensure storage in a dry place because liquid PEGs 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 PEG 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 pro longed 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).
PEGs 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 PEGs 800 to 8000 in the molten state is in stainless steel or aluminium containers fitted with an external, heating coll.
The storage temperature 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.
CARBOWAX Polyethylene Glycol (PEG) 8000 by Dow is PEG-180-based mold release agent and plasticizer.
It possesses lubricity and humectant properties.
It maintains wet-tack strength.
It is used in pressure sensitive and thermoplastic adhesives.
CARBOWAX Polyethylene Glycol (PEG) 8000 meets the requirements for use under food additive regulations for indirect use as components of articles intended for use in contact with food.
Polyglykol 8000 P
PEG-180
Polyglykol 8000 P is a polethylene glycol with a mean molecular weight of 8000.
It is a solid in powder form.
Benefits
Good solubility in water
Very low water content
Compatible with hard water
Non-volatile
Outstanding toxicological safety