Oral Liquid Self-nanoemulsion of Nebivolol: Formulation and In-Vitro Characterization for Dissolution Rate Enhancement

Nebivolol is a unique selective beta-blocker used for the treatment of several chronic cardiovascular diseases. It has poor solubility with low bioavailability (12%). Accordingly, this study improved nebivolol dissolution performance, and hence its oral bioavailability by preparation as self-nanoemulsion (SNE). Method: Saturation solubility in various semisynthetic oils and emulsification efficiency were performed to select proper SNE vehicle combination. Twelve formulas were prepared by varying the proportion of selected mixture. Moreover, proper and adequate in-vitro characterization tests were conducted to select the best formula. Results: The obtained results showed that imwitor 988, cremophor-EL, and propylene glycol (PG) mixture was provided satisfactory nanoemulsion region upon titration with water to be further loaded with lipophilic drugs. The prepared formulas with good stability under stressful conditions revealed a dramatically higher drug releasing rate than a plain drug suspension. The optimum nebivolol SNE could be attained at 10% imwitor:45% cremophor:45% PG w/w combination. This formula (A1) could rapidly form nanoemulsion under gentle agitation with 20.3nm ± 0.3 droplets size and polydispersibility index 0.196 ± 0.01, as confirmed by TEM. It also revealed three times enhancement in drug-releasing rate compared to pure nebivolol. Conclusion: Thus, the developed formula can be utilized as a nanocarrier for oral delivery of nebivolol with good solubilization capacity, higher dissolution rate, and simple manufacturing requirements.