In Vitro Characterization of the Percutaneous Absorption of Lorazepam into Human Cadaver Torso Skin, Using the Franz Skin Finite Dose Models

Objective: Lorazepam is a sedative that may be used for the management of anxiety, insomnia, and chemotherapy-induced nausea and vomiting. Lorazepam can be incorporated into transdermal bases such as Lipoderm, referred to as Phospholipid Base, for drug delivery across the skin. The purpose of this study is to characterize the percutaneous absorption of lorazepam 5 mg/g in Phospholipid Base, when applied to human cadaver torso skin, in vitro, using the Franz skin finite dose model. Methods: The percutaneous absorption of lorazepam was evaluated using ex vivo human cadaver torso skin from 3 donors. The skin from each donor was cut into small sections to fit on nominal 2 cm2 Franz diffusion cells. A nominal volume equivalent to 5 mg formulation/cm2/skin section was then applied to a 2 cm2 dosing surface of 3 replicate skin sections for each donor. At predetermined time points (0, 2, 4, 8, 12, 24, 32, and 48 hr), the receptor solution within each chamber was removed, replaced with fresh receptor solution, and an aliquot of 6 mL was saved for analysis. Mean values for lorazepam total absorption, rate of absorption, skin content, and surface wash were quantified via HPLC analysis. Results: Lorazepam mean total absorption was 8.38% ± 4.37, with a rise to peak rate of absorption at approximately 30 hr following dose application. Lorazepam was also found within the dermis and epidermis at 0.22% ± 0.02 and 3.65% ± 1.29 of the applied dose, respectively. Conclusion: Results show that Phospholipid Base can facilitate the percutaneous absorption of lorazepam. This study’s findings may be helpful when justifying the viability of using Phospholipid Base as a vehicle for the transdermal delivery of lorazepam and could potentially be useful for practitioners and pharmacists considering the skin as an alternative route for the delivery of lorazepam.