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 acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

of ''N'',''N''-dimethylalanine and dodecanol, although as of now the structural formula shows an ester with

decanol 1-Decanol is a straight chain fatty alcohol with ten carbon atoms and the molecular formula C10H21OH. It is a colorless to light yellow viscous liquid that is insoluble in water and has an aromatic odor. The interfacial tension against water at 20 ...

(C10) instead. DDAIP is typically formulated as its hydrochloride

salt In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural crystalline mineral, salt is also known as r ...

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

amphiphilic In chemistry, an amphiphile (), or amphipath, is a chemical compound possessing both hydrophilic (''water-loving'', polar) and lipophilic (''fat-loving'', nonpolar) properties. Such a compound is called amphiphilic or amphipathic. Amphiphilic c ...

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.

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 chemical substance, substance, the solute, to form a solution (chemistry), solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form su ...

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. They may be used to enhance the active ingredient’s therapeutic properties; to facilitate drug absorption; to reduce viscosity; to enhance solubility; to i ...

currently used in the topical drug Vitaros, an alprostadil

vasodilator Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wal ...

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, onychomycosis, fungal nail infections, and ringworm including jock itch and athlete's foot. It is either oral adminis ...

antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as ...

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. Fingernails may be affected, but it is ...

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 In biochemistry, an esterase is a class of enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis (and as such, it is a type of hydrolase). A wide range of different esterases exist that differ ...

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 sid ...

; and dodecanol 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 triglyceride, medium-chain fatty acids. It is a bright white, powdery solid with a faint odor of Piment ...

, both naturally occurring compounds already present in the body.

References

{{reflist Excipients Amino acid derivatives Carboxylate esters Decyl esters