Chemical Properties
Yellowish, waxy mass.
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.
