DDAIP

DDAIP

Systematic (IUPAC) name
2-Dimethylaminopropionic acid dodecyl ester
Clinical data
Pregnancy cat.	?
Legal status	?
Pharmacokinetic data
Bioavailability	<1% (topical)
Protein binding	>99%
Metabolism	Esterase mediated
Half-life	5 hours
Excretion	Urinary
Identifiers
CAS number	224297-43-2 259685-49-9 (HCl)
ATC code	?
UNII	6679UF28DO Y
Synonyms	Dodecyl 2-N,N-dimethylaminopropionate; Dodecyl-2-(dimethylamino)propionate; N,N-Dimethylalanine dodecyl ester
Chemical data
Formula	C17H36ClNO2
Mol. mass	321.93 g/mol
SMILES	eMolecules & PubChem
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DDAIP is a pharmaceutical ingredient added to topical products to increase penetration through the skin. Chemically, DDAIP is an ester of 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.^[1]

Mechanism of action

DDAIP is a permeation enhancer^[2] 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.^[3] It can also improve the solubility of compounds resulting in enhanced drug permeation.^[4]

Clinical use

DDAIP.HCl is a functional non-active excipient currently used in the topical drug Vitaros, an alprostadil vasodilator cream used to treat erectile dysfunction. It is also used in MycoVa,^[5] a terbinafine antifungal nail lacquer for onychomycosis 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 esterases 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.

References

1. ^ "Patent". Crystalline salts of dodecyl 2-(N,N-dimethylamino)-propionate patent. http://www.patentstorm.us/patents/6118020/description.html. Retrieved 11 March 2011. 
2. ^ Das, Debanjan; John Augustine, andMarcel Langenauer. "Overcoming the Skin Barrier by Chemical Enhancements: A Formulator’s Perspective". SP Formulations, LLC. 
3. ^ Hadgraft, J (2001). "Modulation of the Barrier Function of the Skin". Skin Pharmacol Appl Skin Physio 14 (Suppl 1): 72–81. doi:10.1159/000056393. PMID 11509910. 
4. ^ Michniak-Kohn, Bozena; Kishore R Shah (March 2011). "Patchless Transdermal Drug Delivery (TDD)". TransDermal: 5–11. 
5. ^ "Apricus Biosciences Reports Additional Analysis Showing That MycoVa Is As Effective For The Treatment Of Nail Fungus As The Current European Standard Of Care For Topical Therapy, Loceryl". The Street. http://www.thestreet.com/story/10978767/1/apricus-biosciences-reports-additional-analysis-showing-that-mycovatm-is-as-effective-for-the-treatment-of-nail-fungus-as-the-current-european-standard-of-care-for-topical-therapy-locerylr.html. Retrieved 16 March 2011.