Development and Evaluation of an Intracutaneous Depot Formulation of Corticosteroids Using Transcutol as a Cosolvent: In-vitro, Ex-vivo and In-vivo rat Studies

Abstract

A topical delivery system has been developed using 50% Transcutol (diethylene glycol monoethyl ether) to decrease the body burden of topically administered dexamethasone and hydrocortisone. The delivery system was evaluated in-vitro using a dissolution apparatus to measure the release of steroid from the gel. In 10 h, 29·6±0–39% dexamethasone and 45·5 ±0·84% hydrocortisone was released from the formulation compared with 23·0 ±0·48 and 39·9 ±0·77%, respectively, from control formulations without Transcutol. Ex-vivo evaluation was made using rat whole skin in a diffusion cell; the amount of steroid reaching the acceptor cell was significantly less from the formulation containing Transcutol compared with controls. There was also a 2-fold increase in the retention of dexamethasone and a 3-fold increase in the retention of hydrocortisone in the skin at the end of the permeation experiments compared with control experiments. In-vivo studies were made using a formulation containing [3H]hydrocortisone applied to rat skin, followed by measurement of total radioactivity in the blood. For the Transcutol formulation the area under the blood concentration-time curve (0–96 h) was 6·06± 1·27 compared with 2·52 ± 0·43 × 106 d min−1 mL−1 h for the control formulation, indicating a 58% reduction in body burden.