Application of Box-Behnken Design in the Preparation, Optimization, and In-Vivo Pharmacokinetic Evaluation of Oral Tadalafil-Loaded Niosomal Film

Benign prostatic hyperplasia (BPH) affects about 90% of men whose ages are over 65. Tadalafil, a selective PDE-5 inhibitor, was approved by FDA for BPH, however, its poor aqueous solubility and bioavailability are considered major drawbacks. This work intended to develop and evaluate oral fast dissolving film containing tadalafil-loaded niosomes for those who cannot receive the oral dosage form. Niosomes were statistically optimized by Box-Behnken experimental design and loaded into a polymeric oral film. Niosomes were assessed for their vesicular size, uniformity, and zeta potential. The thickness, content uniformity, folding endurance, tensile strength, disintegration time, and surface morphology were evaluated for the prepared polymeric film. The optimized niosomes revealed high entrapment efficiency (99.78 +/- 2.132%) and the film was smooth with good flexibility and convenient thickness (110 +/- 10 mu m). A fast release of tadalafil was achieved within 5 min significantly faster than the niosomes-free drug film. The in-vivo bioavailability in rats established that the optimized niosomal film enhanced tadalafil systemic absorption, with higher peak concentration (C-max = 0.63 +/- 0.03 mu g/mL), shorter T-max value (0.66-fold), and relative bioavailability of 118.4% compared to the marketed tablet. These results propose that the oral film of tadalafil-loaded niosomes is a suitable therapeutic application that can be passed with ease to geriatric patients who suffer from BPH.

Automated summary

This study developed and evaluated an oral fast dissolving film containing tadalafil-loaded niosomes for the treatment of benign prostatic hyperplasia (BPH). The optimized niosomes showed high entrapment efficiency and the film had desirable characteristics. The tadalafil-loaded niosomal film demonstrated faster release and enhanced bioavailability compared to the marketed tablet.