Bassam B. Damaj

Enhanced in vitro transbuccal drug delivery of ondansetron HCl.

The effect of chemical enhancers and iontophoresis on the in vitro transbuccal delivery of 0.5% ondansetron HCl (ODAN HCl) was investigated using porcine buccal tissue. The chemical enhancers used were dodecyl 2-(N,N-dimethyl amino) propionate (DDAIP), its HCl salt dodecyl-2-(N,N-dimethylamino) propionate hydrochloride (DDAIP HCl), N-(4-bromobenzoyl)-S,S-dimethyliminosulfurane (Br-iminosulfurane), and azone. This study demonstrated that anodal iontophoresis at 0.1, 0.2 and 0.3 mA current intensity significantly increased transbuccal delivery of ODAN HCl 3.3-fold, 5.2-fold and 7.1-fold respectively, compared to control. DDAIP HCl provided significantly higher transbuccal delivery of ODAN HCl than did DDAIP, azone and Br-iminosulfurane. It was found that DDAIP HCl in water significantly enhanced drug permeability (920 μg/cm(2)) compared to DDAIP HCl in propylene glycol (PG) (490 μg/cm(2)) during 24h. It was also found that 5% (w/v) DDAIP HCl in water alone provided higher permeation flux (29.3 μg/cm(2)/h) than iontophoresis alone at 0.3 mA (22.8 μg/cm(2)/h) during the same 8h treatment. A light microscopy study showed that treatment with chemical enhancers and iontophoresis did not cause major morphological changes in the buccal tissue. EpiOral™ MTS cytotoxicity studies demonstrated that DDAIP HCl at less than 5% (w/v) in water did not have significant detrimental effects on the cells.

Enhancing the Skin Flux of Tolnaftate Utilizing the Novel Excipient, Dodecyl-2-N,NDimethylaminopropionate (DDAIP)

Enhancing the Skin Flux of Tolnaftate Utilizing the Novel Excipient, Dodecyl-2-N, NDimethylaminopropionate (DDAIP) nPenetration of drug through the stratum corneum to reach the underlying epidermal and dermal layers is a critical step for effective therapy by the topical route. To enhance permeation, various penetration enhancers have been utilized in combination with active drugs. The novel excipient, dodecyl-2-N,Ndimethylaminopropionate (DDAIP), was utilized to assess the epidermal penetration of tolnaftate. Tolnaftate, an anti-fungal agent, is approved as an over-the-counter (OTC) product for the treatment of superficial fungal infections including, athlete’s foot, ringworm and jock itch. Utilizing human cadaver skin mounted on Franz cells, tolnaftate skin flux was evaluated with and without the presence of DDAIP. Over a 24-hour period, DDAIP at a concentration of 0.5% enhanced tolnaftate permeation through human cadaver skin relative to the marketed tolnaftate formulation (1%). Increased tolnaftate penetration may decrease the number of applications and treatment duration required for dermatophyte therapy.

The Novel Excipient, Dodecyl-2-N, N-dimethylaminopropionate Hydrochloride (DDAIP-HCl) Improves the Flux of Minoxidil in Human Skin

Transdermal delivery of topically applied compounds is limited by the stratum corneum (SC) protective barrier. Penetration enhancers have been employed to perturb the skin barrier and enhance the transdermal flux of drugs. The novel excipient, dodecyl-2-N, N-dimethylaminopropionate hydrochloride (DDAIP-HCl), was evaluated for penetration activity of minoxidil in human cadaver skin. Minoxidil skin flux through human cadaver skin mounted on Franz cells was investigated with and without the presence of DDAIP-HCl. Enhanced minoxidil permeation levels were observed with DDAIP-HCl at concentrations of 0.05% and 0.5% through human cadaver skin relative to the formulation of the marketed hair loss product Rogaine® (5% minoxidil) over a 24-hour period. Increased minoxidil penetration may lead to a better efficacy and clinical response in the treatment of male pattern hair loss or Androgenetic alopecia.