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Macrogol 15 Hydroxystearate Excipient | Uses, Suppliers, and Specifications
Macrogol 15 Hydroxystearate is also known as Polyethylene glycol-15-Hydroxystearate, a synthetic non-ionic surfactant obtained by alkoxylation of 12-Hydroxystearic acid. It contains about 30% free macrogols. Macrogol 15 Hydroxystearate occurs as a yellowish-white, almost odourless waxy mass or paste at room temperature, which becomes liquid at approximately 30oC.
Pharmacopoeial Compliance: USP-NF; Ph.Eur; B.P
Synonyms and Trade Names: Macrogol 15 Hydroxystearate; Polyoxyl 15 Hydroxystearate; Polyethylene Glycol 660 12-Hydroxystearate; Polyethylene Glycol-15-Hydroxystearate; Solutol® HS 15; Kolliphor® HS 15; CRODASOL® HS HP
Uses and Applications: Dissolution Enhancer; Nonionic Surfactant; and Solubilising Agent
Macrogol 15 Hydroxystearate is also known as Polyethylene glycol-15-Hydroxystearate, a synthetic non-ionic surfactant obtained by alkoxylation of 12-Hydroxystearic acid. It contains about 30% free macrogols. Macrogol 15 Hydroxystearate occurs as a yellowish-white, almost odourless waxy mass or paste at room temperature, which becomes liquid at approximately 30oC.
Pharmacopoeial Compliance: USP-NF; Ph.Eur; B.P
Synonyms and Trade Names: Macrogol 15 Hydroxystearate; Polyoxyl 15 Hydroxystearate; Polyethylene Glycol 660 12-Hydroxystearate; Polyethylene Glycol-15-Hydroxystearate; Solutol® HS 15; Kolliphor® HS 15; CRODASOL® HS HP
Uses and Applications: Dissolution Enhancer; Nonionic Surfactant; and Solubilising Agent
| Chemical Name | 2-Hydroxyethyl-12-hydroxyoctadecanoate |
| CAS Registration Number | [70142-34-6] |
| Empirical Formula | C20H40O4 |
| Molecular Weight | 334.53 |
| EC Number | TBC |
| UNII Code (FDA) | 71YMM1X75O |
Macrogol 15 hydroxystearate (synonyms: Polyethylene glycol-15-hydroxystearate. It is a non-ionic surfactant obtained by reacting 12-hydroxystearate with 15 moles of ethylene oxide. Thus, it belongs to the same class as polyethylene glycol esters of fatty acids. In the Ph.Eur, Macrogol 15 hydroxystearate is described as a mixture of monoesters and diesters of 12-hydroxystearic acid and polyethylene glycols obtained by the ethoxylation of 12-hydroxystearic acid. It contains 15 moles of ethylene oxide per mole of 12-hvdroxystearic acid. It contains about 30% free polyethylene glycols.
Macrogol 15-Hydroxystearate was developed as a sequel to Polyoxyethylene castor oil derivatives (Polyoxyl 40 hydrogenated castor oil and Polyoxyl-35 castor oil), which were known to produce elevated histamine levels. In order to help avert this, BASF and Wyeth developed a new analogue in which Castor oil was replaced with 12-hydroxystearic acid and reacted with Polyethylene glycol 30. The resulting excipient was termed Solutol® HS 15.
Subsequent studies showed Macrogol 15-Hydroxystearate to be safe in various animal toxicity models, including reduced histamine levels compared with Polyoxyethylene castor oil derivatives. A drug master file was filed with the US FDA in 1992, and the material has since been used in several commercial products.
Macrogol 15 hydroxystearate occurs a yellowish-white, almost odourless waxy mass or paste at room temperature, which becomes liquid at approximately 30oC.
| Form | Semi-solid (waxy mass or paste) |
| Appearance | Yellowish-white |
| pH (10% aqueous solution) | 6-7 (20 oC) |
| Critical micelle concentration | 0.005-0.02% |
| Density | 1.03 g/ml |
| Flash point | 272 oC |
| HLB value | 14-16 |
| Ignition temperature | 360 oC |
| Solidification temperature | 25 – 30 oC |
| Solubility | Soluble in water, ethanol (95%) and isopropanol. Insoluble in mineral oil. Water solubility decreases with an increase in temperature |
| Viscosity | 12 mPa s (30% w/v aqueous solution at 25 oC)
73 mPa s (30% w/v aqueous solution at 60 oC) |
Macrogol 15 hydroxystearic is an approved excipient (previously, a novel excipient). It is listed in the USP-NF; Ph.Eur and B.P and approved for use in parenteral pharmaceutical preparations. Macrogol 15 hydroxystearate is listed in the US FDA Inactive Ingredients database (parenteral formulations) and a Type IV DMF is maintained by BASF (US DMF #9501).
| USP-NF | Ph.Eur | |
| Name | Polyoxyl 15 Hydroxystearate | Macrogol 15-Hydroxystearate |
| Authorised use | Excipient | Excipient |
| Definition | specified | specified |
| Identification
A B C |
A B C |
specified |
| Characters
Appearance Solubility |
n/a | specified |
| Composition | specified | n/a |
| Appearance of solution | n/a | specified |
| Acid value | ≤ 1.0 | ≤ 1.0 |
| Hydroxyl value | 90 -110 | 90 -110 |
| Iodine value | ≤ 2.0 | ≤ 2.0 |
| Peroxide value | ≤ 5.0 | ≤ 5.0 |
| Saponification value | 53-63 | 53-63 |
| Free macrogols | 27.0-39.0% | 27.0-39.0% |
| Ethylene oxide | ≤ 1 ppm | ≤ 1 ppm |
| Dioxane | ≤ 50 ppm | ≤ 50 ppm |
| Nickel | ≤ 1 ppm | ≤ 1 ppm |
| Water | ≤ 1% | ≤ 1% |
| Total ash | ≤ 0.3% | ≤ 0.3% |
| Assay | n/a | n/a |
| Labelling | n/a | n/a |
Key: n/a Specification is not listed
*All claims with respect to conformity are subject to our Terms and Conditions. No express or implied warranty is made for specific properties or fitness for any particular application or purpose.
Macrogol 15 hydroxystearate is a nonionic surfactant; solubilizing agent; stabilizing agent and dissolution rate enhancer. It is a highly effective solubilizer and emulsifying agent of choice for formulating poorly soluble drug substances both for parenteral and oral dosage forms.
Owing to its ability to form spherical micelles, Macrogol 15 hydroxystearate is utilised in the formulation of parenteral drug products, particularly during preclinical development stages. The benefits it offers include:
- Low histamine release, reduces side-effects
- Thermal stability, suitable for sterilization
- Lower haemolytic activity compared to other Polyoxyethylene-based surfactants
- Monographed in Ph. Eur. and USP-NF
Macrogol 15 hydroxystearate is highly efficient at solubilizing hydrophobic drug substances, such as fat-soluble vitamins. When used at a concentration of 20%, Macrogol 15 hydroxystearate enhances the water solubility of candidate drug substances several fold, depending on the physicochemical characteristics of the solute molecules.
Macrogol 15-hydroxystearate is a relatively new non-ionic surfactant that has been shown to have low toxicity in vivo. Macrogol 15-hydroxystearate has been shown to be safe in different animal toxicity models with reduced histamine levels. It is currently approved for parental applications in the USA, Canada, the EU and UK.
Toxicology: LD50 (rat, oral): >20g/kg; LD50 (rat, IV): 1.0-1.47g/kg. Macrogol 15-hydroxystearate has not been demonstrated as mutagenic in bacteria, mammalian cell cultures and mammals.
A summary report by the European Medicines Agency on the current understanding of Macrogol 15-hydroxystearate’s pharmacological and toxicological effects can be found through this link.
Storage & Handling Requirements
A sustainability score for Macrogol 15-hydroxystearate has not been provided.
[1] H. Bley, B. Fussnegger, R. Bodmeier, Characterization and stability of solid dispersions based on PEG/polymer blends, international journal of pharmaceutics, 390 (2010) 165-173.
[2] M.H. Aburahma, S.M. Badr-Eldin, Compritol 888 ATO: a multifunctional lipid excipient in drug delivery systems and nanopharmaceuticals, Expert opinion on drug delivery, 11 (2014) 1865-1883.
[3] P.J.C. Sheskey, Walter G; Cable, Colin G, Handbook of Pharmaceutical Excipients – 8th Edition, Pharmaceutical Development and Technology, 18 (2017) 544-544.
[4] K. Viaud-Quentric, S. Lefranc-Jullien, L. Feraille, P.P. Elena, Long-term tolerance of preservative-free eye drops containing macrogol hydroxystearate as an excipient, journal francais d ophtalmologie, 39 (2016) 156-163.
[5] A.V. Gore, K.S. Warner, C.P. Pujara, R.S. Graham, A.P. Parashar, M.-L. Lee, R.S. Jordan, S. Likitlersuang, MACROGOL 15 HYDROXYSTEARATE FORMULATIONS, 2012.
Buy Secondary Reference Standards Certified to Ph.Eur and USP-NF
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