• Effect of barrier integrity on topical/transdermal delivery of diclofenac sodium via iontophoresis

      Dandekar, Amruta; Kale, Madhura S.; Mahadevabharath, R. Somayaji; Garimella, Harsha T.; Banga, Ajay K. (2021)
      Introduction: Application of a drug product on compromised skin may result in altered drug delivery leading to potential systemic toxicity. In this study, we investigated the effect of barrier integrity on the topical and transdermal delivery of brand: generic pair of diclofenac sodium (model anti-inflammatory drug) via iontophoresis. Methods: In vitro drug permeation studies were performed on normal and compromised skin using vertical Franz diffusion cells. A compromised skin model was created using ten tape strips on dermatomed human skin. We compared marketed brand and generic formulations of diclofenac sodium (Voltaren� and 1% diclofenac sodium topical gel by Amneal) via cathodal iontophoresis (0.5 mA/cm2; 2h followed by passive delivery till 6h) using 700 �L of formulation. Results/Conclusion: No significant difference observed between brand and generic formulations for delivery of diclofenac sodium via normal (149.78�18.43�g/cm2(brand);145.53�12.61�g/cm2(generic)) and compromised skin (233.13�8.32 �g/cm2(brand); 242.07�11.17 �g/cm2(generic)). The total delivery of diclofenac was significantly higher for the brand-generic pair into and across compromised skin as compared to normal skin indicating the effect of barrier integrity on delivery of diclofenac sodium. However, there was no significant difference in skin delivery of diclofenac sodium for normal (94.18�15.08 �g/cm2 (brand); 76.97�14.15 �g/cm2 (generic)) and compromised skin (76.74�8.75 �g/cm2 (brand); 72.36�5.18 �g/cm2 (generic)).
    • Topical and Transdermal Iontophoretic Delivery of Methotrexate in Healthy and Psoriatic Human Skin

      Vora, Deepal; Somayaji, Mahadevabharath R.; German, Carrie; Banga, Ajay K. (2021)
      Psoriasis is a condition of the skin which involves scales, dry patches, and inflammation. Methotrexate (logP: -0.236, MW: 454.44 g/mol) is administered orally or intravenously to treat psoriasis. The first pass metabolism and systemic side effects associated can be avoided by transdermal delivery. We investigated the iontophoretic delivery of methotrexate using healthy and psoriatic human skin to understand the effect of skin�s disease condition on topical and transdermal delivery. In vitro permeation testing using vertical Franz diffusion cell were conducted. Cathodal iontophoresis (0.5 mA/sq.cm for 4 h) delivered a significantly higher total amount of methotrexate into the skin and receptor when compared to that delivered by passive diffusion and anodal iontophoresis. A current density of 0.2 mA/sq.cm using cathodal iontophoresis and 10mg/mL donor concentration was optimized to obtain the target delivery through healthy human skin. There was no significant difference in receptor delivery for psoriatic skin as compared to healthy skin, while significantly higher methotrexate delivery in skin was observed for psoriatic skin as compared to healthy skin. Thus, cathodal iontophoresis delivered a significantly higher total amount of methotrexate as compared to passive diffusion and anodal iontophoresis. Significantly higher delivery in skin and hence significantly higher total delivery was observed for psoriatic skin as compared to healthy skin.