Development and characterization of orally disintegrating films of Nebivolol as complex with Sulfobutylether-β-cyclodextrin

Low water solubility and extensive hepatic first-pass metabolism limit oral bioavailability of Nebivolol hydrochloride (NEB), a new-generation β-blocker agent effective in hypertension treatment. To overcome such issues, a combined strategy was applied, based on the development of orally disintegrating films (ODFs) loaded with NEB as SBEβCD complex. This approach exploits both the SBEβCD solubilizing power and the fast drug dissolution in the oral cavity provided by ODF. Preformulation studies allowed to select the best combinations of film-forming polymers (PVA in mixture with Na alginate or HPMC) and plasticizer (PEG 400) to obtain ODFs with the desired properties. Loading of selected ODF formulations with NEB-SBEβCD complex significantly increased its dissolution rate: >50 % drug dissolved in simulated saliva after 5′ and 100 % in simulated gastric medium within 30’. In contrast, the plain drug achieved only 30 % and 70 % dissolution, respectively. This should enhance the drug fraction absorbed in the pre-gastric tract, limiting hepatic first-pass metabolism. Moreover, SBEβCD caused a significant reduction of the film disintegration time, due to the higher water-affinity of the drug-CD complex than free drug. Finally, the drug entrapment within the CD cavity should prevent palatability problems related to drug bitter taste, avoiding addition of flavoring agents.