DDAIP

DDAIP
Clinical data
Other namesDodecyl 2-N,N-dimethylaminopropionate; Dodecyl-2-(dimethylamino)propionate; N,N-Dimethylalanine dodecyl ester
Pharmacokinetic data
Bioavailability<1% (topical)
Protein binding>99%
MetabolismEsterase mediated
Elimination half-life5 hours
ExcretionUrinary
Identifiers
IUPAC name
  • 2-Dimethylaminopropionic acid dodecyl ester
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC17H36ClNO2
Molar mass321.93 g·mol−1
3D model (JSmol)
SMILES
  • CCCCCCCCCCCCOC(=O)C(C)N(C)C
InChI
  • InChI=1S/C17H35NO2/c1-5-6-7-8-9-10-11-12-13-14-15-20-17(19)16(2)18(3)4/h16H,5-15H2,1-4H3
  • Key:HSMMSDWNEJLVRY-UHFFFAOYSA-N
  (verify)

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.[1]

Mechanism of action

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

Clinical use

DDAIP hydrochloride is a functional inactive 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 5,000 patients have been exposed to this compound with no serious adverse events recorded. DDAIP 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. ↑ US 6118020, Buyuktimkin S, Buyuktimkin N, "Crystalline salts of dodecyl 2-(N,N-dimethylamino)-propionate", issued 12 September 2000, assigned to Nexmed Holdings Inc
  2. ↑ Das D, Augustine J, Langenauer M. "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 Pharmacology and Applied Skin Physiology. 14 Suppl 1 (Suppl 1): 72–81. doi:10.1159/000056393. PMID 11509910. S2CID 33920480.
  4. ↑ Michniak-Kohn B, Shah KR (March 2011). "Patchless Transdermal Drug Delivery (TDD)". TransDermal: 5–11.
  5. ↑ GlobeNewswire. "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. Archived from the original on 4 March 2016. Retrieved 16 March 2011.
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