Octadecanoic acid, 12-hydroxy-, polymer with .alpha.-hydro-.omega.-hydroxypoly(oxy-1,2-ethanediyl)

Chemical properties

Yellowish, waxy mass.

Chemical properties

Macrogol 15 hydroxystearate is a yellowish-white, almost odorless waxy mass or paste at room temperature, which becomes liquid at approximately 30°C.

The Uses of Octadecanoic acid, 12-hydroxy-, polymer with .alpha.-hydro-.omega.-hydroxypoly(oxy-1,2-ethanediyl)

Non-ionic surfactant.

The Uses of Octadecanoic acid, 12-hydroxy-, polymer with .alpha.-hydro-.omega.-hydroxypoly(oxy-1,2-ethanediyl)

Polyethylene Glycol 15-Hydroxystearate is a polymeric surfactant.

Production Methods

Macrogol 15 hydroxystearate is produced by reacting 15 moles of ethylene oxide with 1 mole of 12-hydroxystearic acid.

Pharmaceutical Applications

Macrogol 15 hydroxystearate is frequently used in preclinical testing of drugs, mainly for IV and other parenteral applications. The solubilizing capacity for some tested drugs (clotrimazole, carbamazepine, 17 β-estradiol, sulfathiazole, and piroxicam) increases almost linearly with increasing concentration of solubilizing agent. This is due to the formation of spherical micelles even at high concentrations of macrogol 15 hydroxystearate. Similarly, tests have revealed that viscosity increases with increasing amount of solubilizer, but the amount of solubilized drugs does not have any additional influence on the kinematic viscosity. Lipid nanocapsules comprising macrogol 15 hydroxystearate and soybean phosphatidylcholine containing 3% docetaxel have been successfully prepared by a solvent-free inversion process.
Macrogol 15 hydroxystearate has been used in the manufacture of aqueous parenteral preparations with vitamin A, D, E and K, and a number of other lipophilic pharmaceutical active agents, such as propanidid, miconazole, alfadolone, and alfaxalone. It is very efficient at solubilizing substances like fat-soluble vitamins and active ingredients of hydrophobic nature. It is also an excellent solubilizer for parenteral use, at a concentration of 20%, and the water solubility of different drugs may be enhanced by a factor of 10–100, depending on the structure of the drug molecule.

Safety

Macrogol 15 hydroxystearate is used in parenteral pharmaceutical preparations in concentrations up to 50% to solubilize diclofenac, propanidid, and vitamin K1. It has also been used in preclinical formulations in preparing supersaturated injectable formulations of water-insoluble molecules. It is generally regarded as a relatively nontoxic and nonirritant excipient.
Macrogol 15 hydroxystearate is reported not to be mutagenic in bacteria, mammalian cell cultures and mammals.
LD50 (dog, IV): >3.10 g/kg
LD50 (mouse, IP): >0.0085 g/kg
LD50 (mouse, IV): >3.16 g/kg
LD50 (rabbit, IV): 1.0–1.4 g/kg
LD50 (rat, oral): >20 g/kg
LD50 (rat, IV): 1.0–1.47 g/kg

Storage

Macrogol 15 hydroxystearate has a high chemical stability. The prolonged action of heat may induce physical separation into a liquid and a solid phase after cooling, which can be reversed by subsequent homogenization. Macrogol 15 hydroxystearate is stable for at least 24 months if stored in unopened airtight containers at room temperature (maximum 25 °C). Aqueous solutions of macrogol 15 hydroxystearate can be heat-sterilized (121°C, 0.21 MPa). The pH may drop slightly during heating, which should be taken into account. Separation into phases may also occur, but agitating the hot solution can reverse this. Aqueous solutions can be stabilized with the standard preservatives used in pharmaceuticals.
Macrogol 15 hydroxystearate should be stored in tightly sealed containers in a dry place.

Regulatory Status

Included in the Canadian List of Acceptable Non-medicinal Ingredients.