부산대학교 도서관

Complexation of carbamazepine with 2-hydroxypropyl-β-cyclodextrin was performed to provide improved formulations of this widely used antiepileptic drug. Based on this approach, liquid dosage forms were configured for both parenteral and oral use. Intravenous administration of an aqueous carbamazepine·2-hydroxypropyl-β-cyclodextrin (CBZ·HPβCD) complex at a CBZ dose of 20 mg/kg was well tolerated and generated high initial drug levels that fell monoexponentially as a function of time, yielding a plasma elimination half-life of 38 min. Oral studies were completed with three preparations: a commercially available tablet and suspension, as well as a CBZ·HPβCD oral solution. Oral administration of tablets gave erratic and slow absorption, leading to maximum CBZ concentrations (Cmax) of <2 µg/mL, which were manifested only at 2.5 h after drug dosing. The absolute bioavailability of CBZ from the tablets was ~25%. Both the suspension and CBZ·HPβCD solution gave a significantly improved profile. Thus, the liquid oral dosage forms approximately doubled the oral bioavailability of CBZ compared with the tablets.