Pharmacokinetic and dissolution profiling of tadalafil formulated with SNEDDS and β-cyclodextrin in fast-dissolving tablets.

Abstract

One of the main challenges in the oral administration of tadalafil is its low water solubility, which limits its bioavailability. The research aims for enhancement of solubility and bioavailability for tadalafil, through comparing effectiveness for inclusion complex of Beta-cyclodextrin (β-CD) with self-nanoemulsifying drug delivery system (SNEEDS). Both approaches were further formulated into fast-dissolving tablets (FDTs) to achieve rapid onset of action. Dissolution studies demonstrated superior drug release from both systems compared to the marketed product, with SNEEDS showing 97.54 ± 1.76% release in 30 min and the β-CD complex exhibiting 92.47 ± 1.23% release in 15 min. SNEDDS tablets showed significantly improved dissolution compared to β-CD-tadalafil complexes. In pharmacokinetic studies on Wistar rats, SNEEDS resulted in a higher AUC of 4420.6 mcg/ml.hr, C-max of 3.95 mcg/ml, and a faster T-max of 4 h, indicating enhanced bioavailability in contrast with both the β-CD complexes and the marketed product. The lipophilic system (SNEEDS) was superior to the hydrophilic system (β-CD inclusion complex) in enhancing tadalafil bioavailability. Despite the lower AUC of developed β-CD complex compared to marketed formulation, increased C-max and faster T-max suggested a rapid onset of action and maximum efficacy. In conclusion, the developed lipophilic system-SNEEDS, significantly enhanced tadalafil bioavailability compared to both the hydrophilic system and the marketed product. The optimized SNEDDS formulation exhibited significantly higher dissolution compared with the β-cyclodextrin complex and marketed tablet. This study demonstrates the possibilities of innovative drug delivery systems, especially the lipophilic SEEDS, to address the difficulties related with poorly water-soluble drugs, offers promising avenue to enhance therapeutic efficacy.