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Polyoxyethylene Hydrogenated Castor Oil Derivatives | Uses, Suppliers, and Specifications
Polyoxyethylene Hydrogenated Castor Oil Derivatives (also known as Polyoxyl hydrogenated Castor oil; Castor oil Hydrogenated Ethoxylated, Polyethylene Hydrogenated Castor oil, Macrogolglycerol Hydroxystearate Derivatives) are a family of synthetic non-ionic surfactants obtained by reacting ethylene oxide and Hydrogenated Castor oil. Individual compounds have different degrees of ethoxylation (moles/Polyethylene glycol units indicated by a number suffix (n). Of these, Polyoxyl 40 Hydrogenated Castor oil and Polyoxyl 60 Hydrogenated Castor oil are the most well known. They are supplied as white to yellowish, semisolid pastes.
Pharmacopoeial Compliance: USP-NF; Ph.Eur; I.P; B.P
Synonyms and Trade Names: Polyoxyethylene Hydrogenated Castor Oil; Polyoxyl Hydrogenated Castor Oil; Hydrogenated Polyoxyl Castor Oil; Macrogolglycerol Hydroxystearate; Ethoxylated Hydrogenated Castor Oil, Polyethylene Glycol Hydrogenated Castor Oil; Polyoxyl 40 Hydrogenated Castor Oil; Polyoxyl 60 Hydrogenated Castor Oil; Arlatone; Cremophor RH, Kolliphor® RH; Eumulgin, Lipocol; Simulsol
Uses and Applications: Emulsifying Agent; Solubilising Agent; Wetting Agent
Description
Polyoxyethylene Hydrogenated Castor oil (also, Polyethylene glycol hydrogenated Castor oil; Castor oil hydrogenated ethoxylated) is a generic name for various closely-related PEGylated Hydrogenated Castor oil derivatives. They are obtained by reacting varying amounts of ethylene oxide with Hydrogenated Castor oil. Individual substances are assigned a numerical suffix (X), representing the number of stoichiometric equivalents of ethylene oxide added to one stoichiometric equivalent of Hydrogenated Castor oil.
As highly effective non-ionic surfactants, Polyoxyethylene Hydrogenated Castor oils are widely used in pharmaceuticals formulations, fragrance products, hair sprays, deodorants, and indoor tanning preparations. The hydrophobic portion of the molecule is represented by the fatty acid esters of glycerol (Glycerol Polyethylene glycol oxystearate, together with fatty acid glycerol polyglycol esters) while the Polyethylene glycol portion represents the hydrophilic portion.
Just like natural glycerides, Polyoxyethylene Hydrogenated Castor oil derivatives occur as complex mixtures made up of related components, primarily Polyethylene glycol conjugates, as well as fatty acid esters of Polyethene glycol and ethoxylated glycerol. Ethoxylation of glycerides occurs not only as an etherification of the free alcohol groups of the glycerides but also as a transesterification, which leads to a net insertion of Polyethylene glycol groups between the Glyceryl and fatty acid components of the glyceride. In addition, a proportion of the ethylene oxide also reacts with other molecules of ethylene oxide, resulting in some Polyethylene glycols remaining unattached to glycerides or acid groups. This is why Hydrogenated Castor oil triglycerides are complex mixtures of structurally related molecules.
In theory, X, the numerical suffix assigned to Polyoxyethylene Hydrogenated Castor oil derivates can vary between 2 and 200, i.e Polyxyl 2, 3, 4, …. 200 Hydrogenated Castor oil. In reality, there are only around 13 different Polyoxyethylene Hydrogenated Castor oil derivatives that we could find available commercially, as shown in the table below.
| Polyoxyl-2 Hydrogenated Castor Oil | Polyoxyl-2 Hydrogenated Castor Oil is a Polyethylene glycol derivative of Hydrogenated Castor Oil with an average of 2 moles of ethylene oxide. It consists of a mixture of the etherification and esterification products of hydrogenated castor oil glycerides and fatty acids from hydrogenated castor oil, with two equivalents of ethylene oxide |
| Polyoxyl-7 Hydrogenated Castor Oil | Polyoxyl-7 Hydrogenated Castor Oil is a Polyethylene glycol derivative of Hydrogenated Castor Oil with an average of 7 moles of ethylene oxide. It consists of a mixture of the etherification and esterification products of hydrogenated castor oil glycerides and fatty acids from hydrogenated castor oil, with seven equivalents of ethylene oxide. |
| Polyoxyl-10 Hydrogenated Castor Oil | Polyoxyl-10 Hydrogenated Castor Oil is a Polyethylene glycol derivative of Hydrogenated Castor Oil with an average of 10 moles of ethylene oxide. It consists of a mixture of the etherification and esterification products of hydrogenated castor oil glycerides and fatty acids from hydrogenated castor oil, with ten equivalents of ethylene oxide. |
| Polyoxyl-16 Hydrogenated Castor Oil | Polyoxyl-16 Hydrogenated Castor Oil is a Polyethylene glycol derivative of Hydrogenated Castor Oil with an average of 16 moles of ethylene oxide. It consists of a mixture of the etherification and esterification products of hydrogenated castor oil glycerides and fatty acids from hydrogenated castor oil, with sixteen equivalents of ethylene oxide. |
| Polyoxyl-25 Hydrogenated Castor Oil | Polyoxyl-25 Hydrogenated Castor Oil is a Polyethylene glycol derivative of Hydrogenated Castor Oil with an average of 25 moles of ethylene oxide. It consists of a mixture of the etherification and esterification products of hydrogenated castor oil glycerides and fatty acids from hydrogenated castor oil, with twenty-five equivalents of ethylene oxide |
| Polyoxyl-30 Hydrogenated Castor Oil | Polyoxyl-30 Hydrogenated Castor Oil is a Polyethylene glycol derivative of Hydrogenated Castor Oil with an average of 30 moles of ethylene oxide. It consists of a mixture of the etherification and esterification products of hydrogenated castor oil glycerides and fatty acids from hydrogenated castor oil, with thirty equivalents of ethylene oxide. |
| Polyoxyl-35 Hydrogenated Castor Oil | Polyoxyl-35 Hydrogenated Castor Oil is a Polyethylene glycol derivative of Hydrogenated Castor Oil with an average of 35 moles of ethylene oxide. It consists of a mixture of the etherification and esterification products of hydrogenated castor oil glycerides and fatty acids from hydrogenated castor oil, with thirty-five equivalents of ethylene oxide. |
| Polyoxyl-40 Hydrogenated Castor Oil | Polyoxyl-40 Hydrogenated Castor Oil is a Polyethylene glycol derivative of Hydrogenated Castor Oil with an average of 40 moles of ethylene oxide. It consists of a mixture of the etherification and esterification products of hydrogenated castor oil glycerides and fatty acids from hydrogenated castor oil, with forty equivalents of ethylene oxide. |
| Polyoxyl-45 Hydrogenated Castor Oil | Polyoxyl-45 Hydrogenated Castor Oil is a Polyethylene glycol derivative of Hydrogenated Castor Oil with an average of 45 moles of ethylene oxide. It consists of a mixture of the etherification and esterification products of hydrogenated castor oil glycerides and fatty acids from hydrogenated castor oil, with forty-five equivalents of ethylene oxide. |
| Polyoxyl-50 Hydrogenated Castor Oil | Polyoxyl-50 Hydrogenated Castor Oil is a Polyethylene glycol derivative of Hydrogenated Castor Oil with an average of 50
moles of ethylene oxide. It consists of a mixture of the etherification and esterification products of hydrogenated castor oil glycerides and fatty acids from hydrogenated castor oil, with fifty equivalents of ethylene oxide. |
| Polyoxyl-60 Hydrogenated Castor Oil | Polyoxyl-60 Hydrogenated Castor Oil is a Polyethylene glycol derivative of Hydrogenated Castor Oil with an average of 60 moles of ethylene oxide. It consists of a mixture of the etherification and esterification products of hydrogenated castor oil glycerides and fatty acids from hydrogenated castor oil, with sixty equivalents of ethylene oxide. |
| Polyoxyl-80 Hydrogenated Castor Oil | Polyoxyl-80 Hydrogenated Castor Oil is a Polyethylene glycol derivative of Hydrogenated Castor Oil with an average of 80 moles of ethylene oxide. It consists of a mixture of the etherification and esterification products of hydrogenated castor oil glycerides and fatty acids from hydrogenated castor oil, with eighty equivalents of ethylene oxide |
| Polyoxyl-100 Hydrogenated Castor Oil | Polyoxyl-100 Hydrogenated Castor Oil is a Polyethylene glycol derivative of Hydrogenated Castor Oil with an average of 100 moles of ethylene oxide. It consists of a mixture of the etherification and esterification products of hydrogenated castor oil glycerides and fatty acids from hydrogenated castor oil, with one hundred equivalents of ethylene oxide |
The Ph.Eur lists all ethoxylated derivatives having between 7 and 6o moles of ethylene oxide. The USP-NF only lists a single monograph for Polyoxyl 40 Hydrogenated Castor oil. Both compendia recognise the complex nature of these substances, describing them as mixtures of trihydroxystearyl glycerol, polyethene hydroxystearates and free glycols. Polyoxyethylene Hydrogenated Castor oil derivatives are supplied as white to yellowish, semisolid pastes.
Chemical Structure & Identifiers
x + y + z = ≈ n
| Chemical Name | Polyethoxylated castor oil |
| CAS Registry Number | [161791 12-61] |
| Empirical Formula | Not specified |
| Molecular Weight | 1119.6338 |
| EC Number | 500-151-7 |
| UNII Code (FDA) | 7YC686GQ8F
02NG325BQG |
Regulatory Status
Several Polyoxyethylene Hydrogenated Castor oil derivatives are available commercially, however not all of them are officially listed in the pharmacopoeia as pharmaceutical excipients. In the Ph.Eur monograph, Polyoxyl Hydrogenated Castor oils are defined as Trihydroxystearyl glycerol ethoxylated with 7 to 60 molecules of ethylene oxide (nominal value). The USP-NF contains a single monograph which corresponds to Polyoxyl 40 Hydrogenated Castor oil. Polyoxyl Hydrogenated Castor oils are included in the FDA Inactive Ingredients Database (covering IV injections and ophthalmic solutions).
Physicochemical Properties
| Polyoxyl 40 Hydrogenated castor oil | Polyoxyl 60 Hydrogenated castor oil | |
| Appearance | Viscous liquid or soft paste | White to yellowish soft or viscous soft paste |
| Acid value | ≤1.0 | ≤1.0 |
| HLB value | 14 – 16 | 15 – 17 |
| Hydroxyl value | 60 – 75 | 50 – 70 |
| Iodine value | ≤1 | ≤1 |
| Saponification value | 50 – 60 | 40 – 50 |
| Water content % | ≤2.0 | ≤2.0 |
| Melting point (oC) | ≈30 | ≈40 |
| Solidification point (oC) | 16 – 26 | – |
| Refractive index | 1.450 ± 0.040 | – |
| pH | 5-7 | 6-7 |
| Viscosity (25 oC) | 20-40 cSt | – |
| Surface tension | 41.9 | 40.4 |
| Critical Micelle Concentration (%) | 0.039 | 0.05 |
Pharmacopeoeal Specifications
| Test | Ph.Eur | USP-NF |
| Official name | Macrogolglycerol Hydroxystearate | Polyoxyl 40 Hydrogenated Castor Oil |
| Authorised use | Excipient | Excipient |
| Definition | specified | specified |
| Identification | A
B C D |
A
B C |
| Characters | specified | n/a |
| Appearance of solution | specified | n/a |
| Alkalinity | specified | n/a |
| Relative density | n/a | n/a |
| Specific gravity | n/a | n/a |
| Congealing temperature | n/a | 16-26oC |
| Viscosity at 25oC | n/a | n/a |
| Water | ≤3.0% | ≤3.0% |
| Total ash | ≤0.3% | n/a |
| Residue on ignition | ≤0.3% | ≤0.3% |
| Heavy metals | ≤10ppm | ≤0.001% |
| Acid value | ≤2.0 | ≤2.0 |
| Hydroxyl value | 57-80 | 60-80 |
| Iodine value | ≤5.0 | ≤2.0 |
| Saponification value | 45-69 | 45-69 |
| Dioxane | ≤10ppm | ≤10 µg/g |
| Ethylene oxide | ≤1ppm | ≤1 µg/g |
| Assay | n/a | n/a |
| Labelling | specified | n/a |
Applications in Pharmaceutical Formulations or Technology
Polyoxyethylene Hydrogenated Castor oil derivatives are synthetic non-ionic surfactants used in liquid oral, topical, and parenteral pharmaceutical formulations where they function as emulsifying agents, solubilizing agents and wetting agents. In cosmetic formulations, Polyoxyl 2, 7, 10, 25, 30, 35, 40 and 60 Hydrogenated Castor oils are used as surfactants in concentrations of up to 50%.
In pharmaceutical products, Polyoxyl 40 Hydrogenated Castor oil is the derivative most commonly encountered. It has been used to solubilise lipidic and/or poorly soluble drugs, including emulsification of fat-soluble vitamins, A, D, E, and K. Polyoxyl 40 Hydrogenated Castor oil has been used to successfully formulate a wide variety of BCS IV hydrophobic drugs and anticancer drugs which had previously eluded conventional formulation efforts.
In veterinary pharmaceuticals, Polyoxyl 40 and 60 Hydrogenated Castor oil is also utilised to emulsify fish oils and oils fats that are incorporated into animal feeds. In this sense, they aid the solubilization of nutritive and therapeutic substances, thereby improving their efficacy.
In personal care products, Polyoxyl 40 Hydrogenated Castor oil is mainly used as a solubilizing agent for flavouring (e.g mouthwashes), perfumes and volatile oils.
Safety and Precautions
Polyoxyethylene Hydrogenated Castor oil derivatives are widely used in a variety of oral, topical, and parenteral pharmaceutical products as well as personal care formulations. They have been studied to determine their safety in a number of acute and chronic toxicity tests in animal models. These studies have shown Polyoxyethylene Hydrogenated Castor oil derivatives to be essentially non-toxic and non-irritant excipients.
Data on toxicokinetics, single-dose and repeated-dose toxicity, reproductive and developmental toxicity, genotoxicity, carcinogenicity, dermal and ocular irritation, and sensitization are available for Polyoxyethylene Hydrogenated Castor oils. Reports of anaphylactic reactions, cardiotoxicity, nephrotoxicity, neurotoxicity and pulmonary toxicity have also been observed in humans and animals following parenteral administration of formulations containing these substances.
Stability and Storage Conditions
Polyoxyl Hydrogenated Castor oil derivatives are stable and non-reactive substances. The assigned shelf-life is 2 years if the material is stored in the original container at 25 oC. Aqueous solutions of Polyoxyl Hydrogenated Castor oil are stable even when exposed to moderate heat stress. Prolonged exposure can cause phase separation although the product can be restored to its original form by homogenization. In an aqueous solution, Polyoxyl Castor oil derivatives remain stable even when electrolytes are present in the solution. A number of organic substances may cause precipitation at certain concentrations, especially compounds containing phenolic hydroxyl groups.
Polyoxyethylene Hydrogenated Castor oil derivatives should be stored in a well-closed, airtight container, protected from light, in a cool, dry place. When handling Polyoxyl Hydrogenated Castor oil derivatives, workers should observe applicable SHEQ protocols appropriate to the circumstances and quantity of material handled. the use of eye protection and gloves are recommended.
Sustainability and Environmental Impact
A sustainability score for Polyoxylated Hydrogenated Castor oil derivates has not been provided.
Manufacturers & Suppliers
- Kolliphor® EL 35
- Kolliphor® RH 40
- Kolliphor® RH 60
- Acrysol® EL 135
- Acrysol® RH 140
- Acrysol® RH 160
- Croduret™ 40
- Croduret™ 60
Additional Resources (Downloads)
References and Literature Used
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