DDAIP is a pharmaceutical ingredient added to

topical A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...

products to increase penetration through the skin. Chemically, DDAIP is an

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...

of ''N'',''N''-dimethylalanine and

dodecanol Dodecanol , or lauryl alcohol, is an organic compound produced industrially from palm kernel oil or coconut oil. It is a fatty alcohol. Sulfate esters of lauryl alcohol, especially sodium lauryl sulfate, are very widely used as surfactants. Sod ...

, although as of now the structural formula shows an ester with decanol (C10) instead. DDAIP is typically formulated as its

hydrochloride In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternative n ...

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quant ...

(DDAIP.HCl). This salt is a white crystalline solid with a melting range of 88-93 °C and is an

amphiphilic An amphiphile (from the Greek αμφις amphis, both, and φιλíα philia, love, friendship), or amphipath, is a chemical compound possessing both hydrophilic (''water-loving'', polar) and lipophilic (''fat-loving'') properties. Such a compo ...

molecule with a pKa of 4.87 that is soluble in water up to about 40% w/v. DDAIP is proprietary to NexMed USA, a subsidiary of

Apricus Biosciences Apricus Biosciences, Inc. is a San Diego based biopharmaceutical company advancing innovative medicines in urology and rheumatology. Apricus Biosciences' first product, Vitaros®, has been approved in Europe and Canada for the treatment of erec ...

Mechanism of action

DDAIP is a permeation enhancer that temporarily changes the permeation dynamics of the lipid bilayer and opens up the tight junctions between skin cells so active drug molecules can be rapidly absorbed through the skin into systemic circulation. It can also improve the

solubility In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solub ...

of compounds resulting in enhanced drug permeation.

Clinical use

DDAIP hydrochloride is a functional inactive

excipient An excipient is a substance formulated alongside the active ingredient of a medication, included for the purpose of long-term stabilization, bulking up solid formulations that contain potent active ingredients in small amounts (thus often referred ...

currently used in the topical drug Vitaros, an

alprostadil Prostaglandin E1 (PGE1), also known as alprostadil, is a naturally occurring prostaglandin which is used as a medication. In infants with congenital heart defects, it is delivered by slow injection into a vein to open the ductus arteriosus unt ...

vasodilator cream used to treat erectile dysfunction. It is also used in MycoVa, a

terbinafine Terbinafine, sold under the brand name Lamisil among others, is an antifungal medication used to treat pityriasis versicolor, fungal nail infections, and ringworm including jock itch and athlete's foot. It is either taken by mouth or applied to ...

antifungal nail lacquer for

onychomycosis Onychomycosis, also known as tinea unguium, is a fungal infection of the nail. Symptoms may include white or yellow nail discoloration, thickening of the nail, and separation of the nail from the nail bed. Toenails or fingernails may be affected, ...

currently in phase-III clinical trials.

Safety

Overall, about 5,000 patients have been exposed to this compound with no serious adverse events recorded. DDAIP is primarily metabolized by

esterase An esterase is a hydrolase enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis. A wide range of different esterases exist that differ in their substrate specificity, their protein structure ...

s on cell surfaces and plasma to ''N'',''N''-dimethylalanine, which is further demethylated to

alanine Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side ...

; and

which is oxidized to

lauric acid Lauric acid, systematically dodecanoic acid, is a saturated fatty acid with a 12-carbon atom chain, thus having many properties of medium-chain fatty acids. It is a bright white, powdery solid with a faint odor of bay oil or soap. The salts and ...

, both naturally occurring compounds already present in the body.

References

{{reflist Excipients Amino acid derivatives Carboxylate esters