DDAIP
Encyclopedia
DDAIP is a pharmaceutical ingredient added to topical
products to increase penetration through the skin. Chemically, DDAIP is an ester
of N,N-dimethylalanine and dodecanol
. DDAIP is typically formulated as its hydrochloride
salt (DDAIP.HCl). This salt is a white crystalline solid with a melting range of 88-93 °C and is an amphiphilic 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
.
of compounds resulting in enhanced drug permeation.
currently used in the topical drug Vitaros, an alprostadil
vasodilator cream used to treat erectile dysfunction. It is also used in MycoVa, a terbinafine
antifungal
nail lacquer for onychomycosis
currently in Phase III clinical trials.
s on cell surfaces and plasma to N,N-dimethylalanine, which is further demethylated to alanine
; and dodecanol
which is oxidized to lauric acid
, both naturally occurring compounds already present in the body.
Topical
In medicine, a topical medication is applied to body surfaces such as the skin or mucous membranes such as the vagina, anus, throat, eyes and ears.Many topical medications are epicutaneous, meaning that they are applied directly to the skin...
products to increase penetration through the skin. Chemically, DDAIP is an ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
of N,N-dimethylalanine and dodecanol
Dodecanol
Dodecanol, also known by its IUPAC name 1-dodecanol or dodecan-1-ol, and by its trivial name dodecyl alcohol and lauryl alcohol, is a fatty alcohol. Dodecanol is a colourless, water insoluble solid of melting point 24 °C and boiling point 259 °C. It has a floral odor...
. DDAIP is typically formulated as its hydrochloride
Hydrochloride
In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid....
salt (DDAIP.HCl). This salt is a white crystalline solid with a melting range of 88-93 °C and is an amphiphilic 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
Apricus Biosciences is a San Diego based pharmaceutical company which develops products utilizing a permeation enhancer, the NexACT drug delivery technology to enable multi-route administration of compounds across numerous therapeutic classes....
.
Mechanism of action
DDAIP is a permeation enhancer that temporarily changes the permeation dynamics of the lipid bi-layer and opens up the tight junctions between skin cells so that active drug molecules can be rapidly absorbed through the skin into systemic circulation. It can also improve the solubilitySolubility
Solubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent. The solubility of a substance fundamentally depends on the used solvent as well as on...
of compounds resulting in enhanced drug permeation.
Clinical use
DDAIP.HCl is a functional non-active excipientExcipient
An excipient is generally a pharmacologically inactive substance used as a carrier for the active ingredients of a medication. In many cases, an "active" substance may not be easily administered and absorbed by the human body; in such cases the substance in question may be dissolved into or...
currently used in the topical drug Vitaros, an alprostadil
Alprostadil
Prostaglandin E1 , known pharmaceutically as alprostadil, is a prostaglandin. It is a drug used in the treatment of erectile dysfunction and has vasodilatory properties.-Sexual dysfunction:...
vasodilator cream used to treat erectile dysfunction. It is also used in MycoVa, a terbinafine
Terbinafine
Terbinafine hydrochloride is a...
antifungal
Antifungal
* Antifungal medication, a medication used to treat fungal infection s such as athlete's foot , ringworm, candidiasis, etc.* Antifungal protein, a protein family* an adjective referring to a fungicide compound...
nail lacquer for onychomycosis
Onychomycosis
Onychomycosis means fungal infection of the nail. It is the most common disease of the nails and constitutes about a half of all nail abnormalities....
currently in Phase III clinical trials.
Safety
Overall, about 5000 patients have been exposed to this compound with no serious adverse events recorded. DDAIP.HCl is primarily metabolized by esteraseEsterase
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, and their biological function.- EC classification/list...
s on cell surfaces and plasma to N,N-dimethylalanine, which is further demethylated to alanine
Alanine
Alanine is an α-amino acid with the chemical formula CH3CHCOOH. The L-isomer is one of the 20 amino acids encoded by the genetic code. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid...
; and dodecanol
Dodecanol
Dodecanol, also known by its IUPAC name 1-dodecanol or dodecan-1-ol, and by its trivial name dodecyl alcohol and lauryl alcohol, is a fatty alcohol. Dodecanol is a colourless, water insoluble solid of melting point 24 °C and boiling point 259 °C. It has a floral odor...
which is oxidized to lauric acid
Lauric acid
Lauric acid , the saturated fatty acid with a 12-carbon atom chain, is a white, powdery solid with a faint odor of bay oil or soap.-Occurrence:...
, both naturally occurring compounds already present in the body.