Development and evaluation of an intracutaneous depot formulation of corticosteroids using Transcutol as a cosolvent: in-vitro, ex-vivo and in-vivo rat studies.
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 x 10(6) d min-1 mL-1 h for the control formulation, indicating a 58% reduction in body burden.
Panchagnula
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Division of Pharmaceutics and Drug Delivery Systems, College of Pharmacy, University of Cincinnati Medical Center, OH 45267.
Ritschel
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WA
D000287:Administration, Topical; D001822:Body Burden; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005026:Ethylene Glycols / Q000494:pharmacology*; D005782:Gels; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012869:Skin Absorption / Q000187:drug effects; D012997:Solvents
D003692:Delayed-Action Preparations; D005026:Ethylene Glycols; D005782:Gels; D012997:Solvents; D003907:Dexamethasone; C010111:carbitol; D006854:Hydrocortisone