Abstract
Clinical efficacy of nebivolol is restricted primarily because of its low aqueous solubility and extensive hepatic metabolism. This study investigated the prospective of enhancing the systemic delivery of nebivolol HCl by formulating nanocrystals impregnated films for the buccal application. Nanocrystals of nebivolol HCl were prepared by acid-base neutralization method. Placebo films (N1-N3) were optimized by varying concentrations of chitosan. Further pure nebivolol HCl and its nanocrystals were incorporated to the films at two levels (2.5 mg/cm(2) and 5 mg/cm(2)). The prepared films (N4-N7) were assessed for physicomechanical properties, swelling, drug release and permeation by standard protocols. Selected films were evaluated in vivo on rabbits. Physicomechanical properties displayed by the prepared films (N4-N7) were found to be adequate for the buccal application. Rapid swelling of films was noticed which would be beneficial and may contribute to immediate and effective bioadhesion with the buccal mucosa. The rate of drug dissolution was rapid and complete in 4 h from nanocrystals embedded films (N6 and N7) when compared to films loaded with pure drug. The permeation data indicates greater transport when drug concentration was higher (Film N7; 36.31 +/- 6.54 mu g/cm(2)/h; p < 0.0001). In vivo data signified rapid absorption (C-max similar to 24 ng/mL) and higher AUC(0-alpha) (similar to 4 00 ng * h/mL) with similar to 2.5 folds improvement in the bioavailability. In conclusion, registered data suggests that the buccal application of nanocrystals embedded film improved the efficacy of nebivolol HCl, and necessitates further clinical studies.