Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2487132 | Journal of Pharmaceutical Sciences | 2009 | 12 Pages |
Abstract
This investigation includes an evaluation of the percutaneous absorption of bupropion (BUP) and hydroxybupropion (BUPOH) in vitro and in vivo. In addition, a carbamate prodrug of BUPOH (ButâBUPOH) was evaluated in vitro. In vitro diffusion studies were conducted in a flowâthrough diffusion cell system. The in vitro mean steadyâstate flux of BUP was significantly higher (pâ<â0.001) compared to BUPOH (320â±â16 nmolâcmâ2âhâ1 vs. 27â±â4 nmolâcmâ2âhâ1). Additionally, a good correlation existed between in vitro and in vivo results. Mean steadyâstate plasma concentrations of 442â±â32 ng/mL and125â±â18 ng/mL were maintained over 48 h after topical application of BUP and BUPOH in hairless guinea pigs in vivo, respectively. Although BUP traversed human skin at rates sufficient to achieve required plasma levels, it is chemically unstable and hygroscopic, and unsuitable for transdermal formulation. On the other hand, BUPOH is stable but its transport across skin is much slower. Alternatively, the prodrug ButâBUPOH was found to be stable, and also provided a 2.7âfold increase in the transdermal flux of BUPOH across human skin in vitro. Thus, ButâBUPOH provides a viable option for the transdermal delivery of BUPOH. © 2008 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 98:583-594, 2009
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Authors
Paul K. Kiptoo, Kalpana S. Paudel, Dana C. Hammell, Raghotham Reddy Pinninti, Jianhong Chen, Peter A. Crooks, Audra L. Stinchcomb,