Chemistry:DDAIP
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| Other names | Dodecyl 2-N,N-dimethylaminopropionate; Dodecyl-2-(dimethylamino)propionate; N,N-Dimethylalanine dodecyl ester |
| Pharmacokinetic data | |
| Bioavailability | <1% (topical) |
| Protein binding | >99% |
| Metabolism | Esterase mediated |
| Elimination half-life | 5 hours |
| Excretion | Urinary |
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| Chemical and physical data | |
| Formula | C17H36ClNO2 |
| Molar mass | 321.93 g·mol−1 |
| 3D model (JSmol) | |
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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 N,N-dimethylalanine and dodecanol, although as of now the structural formula shows an ester with decanol (C10) instead. 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
- ↑ Buyuktimkin S, Buyuktimkin N, "Crystalline salts of dodecyl 2-(N,N-dimethylamino)-propionate", US patent 6118020, issued 12 September 2000, assigned to Nexmed Holdings Inc
- ↑ "Overcoming the Skin Barrier by Chemical Enhancements: A Formulator's Perspective". SP Formulations, LLC.
- ↑ "Modulation of the barrier function of the skin". Skin Pharmacology and Applied Skin Physiology 14 (Suppl 1): 72–81. 2001. doi:10.1159/000056393. PMID 11509910.
- ↑ "Patchless Transdermal Drug Delivery (TDD)". TransDermal: 5–11. March 2011.
- ↑ "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". GlobeNewswire. 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.
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