Abstract-The aim of this study was to test the feasibility of transdermal delivery of elvitegravir (EVG), a potent HIV-1 integrase inhibitor for development of a transdermal patch of the same for HIV prophylaxis. The targeted skin permeation flux was about 25 μg/cm2/h. In vitro drug permeation studies were performed using vertical Franz diffusion cells. Passive permeation of EVG through dermatomed human skin and human epidermis was investigated. Effect of 5% w/w oleic acid, 25% v/v ethanol, 40% w/w dimethyl sulfoxide, 10% w/w lauric acid, and combination of 20% w/w dimethyl sulfoxide, 10% w/w oleic acid, and 5% w/w lauric acid in propylene glycol on the permeation of EVG through human epidermis was evaluated. Phosphate buffered saline (pH 7.4) containing 10% v/v propylene carbonate and/or polyethylene glycol 400 was used as the receptor. Sampling of the receptor was performed at pre-determined time points for 168 h and analysis was done using HPLC. Permeation of EVG through dermatomed human skin and human epidermis from its free solution in propylene glycol was found to be 5.51 ± 3.48 μg/cm2 and 21.14 ± 3.23 μg/cm2 (control), respectively after 168 h. Oleic acid and dimethyl sulfoxide significantly enhanced the permeation of EVG to 235.97 ± 49.06 μg/cm2 and 700.01 ± 107.03 μg/cm2, respectively, through human epidermis in comparison to the control group (p<0.05). Overall, even with the use of different enhancers or their combination, the targeted permeation flux was not achieved. EVG was thus, not considered further for patch development.
Dr. Hina Umbreen, Dr. Iqra Sadaf, Dr. Sidra Tahir
Elvitegravir (EVG), Potent HIV-1, HIV prophylaxis