Functional Category
Alkalizing agent; emulsifying agent.
Applications in Pharmaceutical Formulation
Diethanolamine is primarily used in pharmaceutical formulations as a buffering agent, such as in the preparation of emulsions with fatty acids. In cosmetics and pharmaceuticals it is used as a pH adjuster and dispersant. Diethanolamine has also been used to form the soluble salts of active compounds, such as iodinated organic acids that are used as contrast media. As a stabilizing agent, diethanolamine prevents the discoloration of aqueous formulations containing hexamethylenetetramine-1,3-dichloropropene salts. Diethanolamine is also used in cosmetics.
Description
Diethanolamine is hygroscopic and light- and oxygen-sensitive; it should be stored in an airtight container, protected from light, in a cool, dry place. See Monoethanolamine for further information.
Incompatibilities
Diethanolamine is a secondary amine that contains two hydroxy groups. It is capable of undergoing reactions typical of secondary amines and alcohols. The amine group usually exhibits the greater activity whenever it is possible for a reaction to take place at either the amine or a hydroxy group. Diethanolamine will react with acids, acid anhydrides, acid chlorides, and esters to form amide derivatives, and with propylene carbonate or other cyclic carbonates to give the corresponding carbonates. As a secondary amine, diethanolamine reacts with aldehydes and ketones to yield aldimines and ketimines. Diethanolamine also reacts with copper to form complex salts. Discoloration and precipitation will take place in the presence of salts of heavy metals.
Safety
Diethanolamine is used in topical and parenteral pharmaceutical formulations, with up to 1.5% w/v being used in intravenous infusions. Experimental studies in dogs have shown that intravenous administration of larger doses of diethanolamine results in sedation, coma, and death. Animal toxicity studies suggest that diethanolamine is less toxic than monoethanolamine, although in rats the oral acute and subacute toxicity is greater.(1) Diethanolamine is said to be heptacarcinogenic in mice and has also been reported to induce hepatic choline deficiency in mice.(2) Diethanolamine is an irritant to the skin, eyes, and mucous membranes when used undiluted or in high concentration. However, in rabbits, aqueous solutions containing 10% w/v diethanolamine produce minor irritation. The lethal human oral dose of diethanolamine is estimated to be 5–15 g/kg body-weight. The US Cosmetic Ingredient Review Expert Panel evaluated diethanolamine and concluded that it is safe for use in cosmetic formulations designed for discontinuous, brief use followed by thorough rinsing from the surface of the skin. In products intended for prolonged contact with the skin, the concentration of ethanolamines should not exceed 5%. Diethanolamine should not be used in products containing N-nitrosating agents.(1) See also Section 18. LD50 (guinea pig, oral): 2.0 g/kg(3) LD50 (mouse, IP): 2.3 g/kg LD50 (mouse, oral): 3.3 g/kg LD50 (rabbit, skin): 12.2 g/kg LD50 (rat, IM): 1.5 g/kg LD50 (rat, IP): 0.12 g/kg LD50 (rat, IV): 0.78 g/kg LD50 (rat, oral): 0.71 g/kg LD50 (rat, SC): 2.2 g/kg