Preparation and evaluation of bicyclol microemulsions for enhanced oral bioavailability

Bicyclol is a novel anti-hepatitis drug used for the treatment of chronic hepatitis B. Bicyclol is insoluble in water and poorly absorbed after oral administration. To date, formulation development studies to improve the in vitro dissolution profiles of bicyclol and the in vivo oral absorption characteristics have not been performed.

To overcome problems associated with the poor solubility and low oral bioavailability of bicyclol, a microemulsion system was prepared and evaluated in vitro and in vivo.

The solubility of bicyclol in various cosurfactants was determined. The optimized premicroemulsion concentrate consisted of transcutol, Tween 20, Cremophor RH 40, propylene glycol monocaprylate and bicyclol (ratio, 50:150:100:150:3). The in vitro solubility and dissolution profiles were determined, and the in vivo oral absorption pharmacokinetics were evaluated in rats (dose, equivalent to 25 mg/kg of bicyclol) in comparison with bicyclol suspended in 0.5% calcium-carboxymethylcellulose (Ca-CMC).

Of various cosurfactants tested, transcutol provided the most significantly increased solubility of bicyclol (>20 mg/ml). Bicyclol was rapidly dissolved from the premicroemulsion concentrate (approximately 80% within 10 min). Consistent with the improved in vitro profiles, the oral absorption of bicyclol was significantly increased for the premicroemulsion concentrate, i.e. AUC and C(max) were increased by 7.7- and 7.2-fold, respectively, over control values. These findings demonstrate that the microemulsion may be a useful drug delivery system to improve the oral bioavailability of bicyclol.