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

Abstract

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 µm). 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 (Cmax = 0.63 ± 0.03 µg/mL), shorter Tmax 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.

Eluxadoline-Loaded Eudragit Nanoparticles for Irritable Bowel Syndrome with Diarrhea: Formulation, Optimization Using Box–Behnken Design, and Anti-Diarrheal Activity

“…For the analysis of particle size, PDI, and zeta potential, the obtained data suggested a quadratic model, which is shown in Table 3 . The difference between adjusted and predicted R 2 values for the investigated responses were less than 0.2, indicating a reasonable degree of agreement in the study design [ 37 ]. The particle size, PDI, and ZP of developed ENPs measured in the range of 286 to 634 nm, 0.263 to 0.321, and 18.8 to 36.1 mV, respectively ( Table 2 ).…”

“…degree of agreement in the study design [37]. The particle size, PDI, and ZP of developed ENPs measured in the range of 286 to 634 nm, 0.263 to 0.321, and 18.8 to 36.1 mV, respectively (Table 2).…”

Propranolol-Loaded Limonene-Based Microemulsion Thermo-Responsive Mucoadhesive Nasal Nanogel: Design, In Vitro Assessment, Ex Vivo Permeation, and Brain Biodistribution

“…Recently, the applications of nanotechnology in drug delivery systems have been expanded with revolutionary effects in the medical and pharmaceutical fields. A breakthrough in nanotechnology has been made possible by lipid-based nanocarriers due to their impressive properties, including biocompatibility, low toxicity, and high versatility [ 20 , 21 , 22 ]. Furthermore, lipid-based nanocarriers can be used to empower the therapeutic potential of active pharmaceutical ingredients that have biopharmaceutical limitations exemplified by poor aqueous solubility, first-pass metabolism, or low stability.…”

Exploring the mechanism of action of Qian Lie Xing Fang during the treatment of benign prostatic hyperplasia via network pharmacology and molecular dynamics simulation analyses

“…Notably, 3g1r is a complex of the type 5 phosphodiesterase inhibitor (PDE-5) protein and small molecules such as finasteride, which is a therapeutic drug used for treating prostate hyperplasia, and has an inhibitory effect on PDE-5. [ 21 ] It can inhibit the conversion of PDE-5 into DHT through testosterone, thereby reducing the concentration of DHT in the serum and prostate. However, long-term medication consumption may lead to common adverse reactions, including sexual dysfunction-related problems, such as erectile dysfunction, abnormal ejaculation, and low libido.…”