Formulation and Optimization of Avanafil Biodegradable Polymeric Nanoparticles: A Single-Dose Clinical Pharmacokinetic Evaluation

Abstract

Avanafil (AVA) is a second-generation phosphodiesterase-5 (PDE5) inhibitor. AVA shows high selectivity to penile tissues and fast absorption, but has a bioavailability of about 36%. The aim was to formulate and optimize AVA-biodegradable nanoparticles (NPs) to enhance AVA bioavailability. To assess the impact of variables, the Box–Behnken design was utilized to investigate and optimize the formulation process variables: the AVA:poly (lactic-co-glycolic acid) (PLGA) ratio (w/w, X1); sonication time (min, X2); and polyvinyl alcohol (PVA) concentration (%, X3). Particle size (nm, Y1) and EE% (%, Y2) were the responses. The optimized NPs were characterized for surface morphology and permeation. Furthermore, a single-oral dose (50 mg AVA) pharmacokinetic investigation on healthy volunteers was carried out. Statistical analysis revealed that all the investigated factors exhibited a significant effect on the particle size. Furthermore, the entrapment efficiency (Y2) was significantly affected by both the AVA:PLGA ratio (X1) and PVA concentration (X3). Pharmacokinetic data showed a significant increase in the area under the curve (1.68 folds) and plasma maximum concentration (1.3-fold) for the AVA NPs when compared with raw AVA. The optimization and formulation of AVA as biodegradable NPs prepared using solvent evaporation (SE) proves a successful way to enhance AVA bioavailability.

Repurposing of Sitagliptin- Melittin Optimized Nanoformula against SARS-CoV-2; Antiviral Screening and Molecular Docking Studies

“…As evident, the zeta potential values decreased with increased drug concentration, while it goes up with increasing MEL concentration and pH. The graphs of the main effects confirm the marked significance of pH on the zeta potential in comparison to the rest of the variables [64][65][66]. For size analysis detailed ANOVA (Table S6).…”

Investigating the Potential of Transdermal Delivery of Avanafil Using Vitamin E-TPGS Based Mixed Micelles Loaded Films

“…Both formulations were applied topically as described in the animal handling section. The AVA concentration and the analysis of the parameters were calculated using the non-compartmental model, utilizing PKsolver [ 31 ]. AVA maximum plasma concentration (C max ), AVA time point of C max (T max ), area under AVA curve from zero to the last measurable point (AUC (0–24) ), area under the first moment plasma curve from time zero to infinity (AUMC (0–inf) ), AVA terminal elimination rate constant (K e ), AVA mean residence time (MRT (0–inf) ), and AVA elimination half-life (t 1/2 ) were calculated.…”

Advances in Nanoparticle Delivery System for Erectile Dysfunction: An Updated Review

“…A clinical study by Aldawsari et al. 26 prepared optimized avanafil-biodegradable polymeric NPs (AVA NPs) loaded in poly (lactic-co-glycolic acid) (PLGA) and evaluated its efficacy in male healthy volunteers ( Table 1 ). Twelve (12) healthy male volunteers age between 25 and 45 years were randomized to receive a single oral dose of AVA PLGA NPs formulation and pure AVA.…”

“…It was concluded that optimization and preparation of AVA as PLGA NPs successfully improved AVA bioavailability. 26 However, further clinical trials are required to confirm the long-term efficacy and safety of AVA-NPs PLGA in male patients with ED.…”

“… 2016 Kurakula et al 25 Polymeric nanoparticles (NPs) poly (lactic-co-glycolic acid) (PLGA) Healthy males Single oral dose 50 mg. NPs PLGA improved avanafil solubility, bioavailability, and reduced the frequency of administration. 2020 Aldawsari et al 26 Sildenafil citrate (SLD) Solid lipid nanoparticles Albino male rats Oral 50 mg/kg. SLD SLNs showed >1.8-fold increase in bioavailability compared to the SLD group.…”