A comparison between direct determination of in vivo dissolution and the deconvolution technique in humans

Aim. The primary objective of this study was to investigate the in vivo dis solution of carbamazepine in humans and to compare it with the dissolution estimated by deconvolution of plasma concentrations as well as the in vitro dissolution. Methods. The in vivo study included six healthy volunteers, and consisted o f two sequential parts. In part 1 the dissolution was measured by perfusing a semi-open segment in the proximal jejunum in humans. In part 2 the volun teers were given a solution of carbamazepine orally. In both parts of the s tudy, plasma samples were collected up to 48 h after administration of the dose. The in vitro dissolution was measured in a flow-through cell using di ssolution medium with and without the addition of bile acids (3 mM). Results. The direct measured in vivo dissolution profile of carbamazepine a nd the deconvoluted profile were found to be similar. The two dissolution p rofiles of carbamazepine obtained in vitro were statistically lower than th e two in vivo dissolution profiles. The higher in vivo dissolution rate is probably due to efficient sink conditions as a consequence of the high perm eability of carbamazepine and more pronounced intestinal motility. Conclusion. The jejunal perfusion system was successfully used for in vivo dissolution measurements of carbamazepine and agreed with the deconvoluted plasma profile regarding rate and extent of dissolution. Single-pass perfus ion is therefore a meaningful tool for further studies of in vivo dissoluti on. (C) 1999 Elsevier Science BN. All rights reserved.