Enhancement of carbamazepine dissolution: in vitro and in vivo evaluation

The absorption of carbamazepine (CBZ) is characterized by being dissolution-rate limited. Thus improvement of its dissolution characteristics may increase its rate and extent of absorption, hence its oral bioavailability. The objective of the work is to enhance the dissolution of CBZ, through utilizing different carriers [polyethylene glycols (PEG), phospholipids, and hydroxypropyl-beta-cylcodextrin (HP beta CD)I. The prepared systems were evaluated in vitro through dissolution testing, X-ray diffraction, and differential thermal analysis (DTA). The screened lead systems were further evaluated in vivo using the rabbit as an animal model. In vitro results showed that the dissolution of CBZ was profoundly enhanced from (1:2) CBZ/PEG(6000) solid dispersion, (10:1) CBZ/L-alpha-dimyristoyl phosphatidyl glycerol coprecipitate, and (1 M:l M) CBZ/HP beta CD complex. X-Ray diffraction and DTA were used to explain any interaction and/or complexation between CBZ and the different carriers. For in vivo evaluation, a parallel design with four groups was adopted, with each group receiving the equivalent of 100 mg CBZ either as one of the three lead prepared systems suspended in water or as Tegretol(R) suspension, the reference standard. Serial blood samples were drawn over 24 h from the marginal ear vein, and plasma samples were analyzed for CBZ and its active metabolite, carbamazepine-10,11-epoxide, CBZE, by HPLC. The in vivo results showed that the extent of absorption of CBZ from its HP beta CD complex was the highest among the systems tested. For all prepared systems, areas under the CBZE concentration-time curve were significantly higher than that resulting after Tegretol(R) suspension. This may be explained by the fact that CBZ is being presented from the Tegretol(R) suspension at a slower rate, with absorption occurring further down the intestine, thus bypassing the liver. (C) 1998 Elsevier Science B.V. All rights reserved.