title: Development and evaluation of avanafil self-nanoemulsifying drug delivery system with rapid onset of action and enhanced bioavailability.
abstract: Utilization of lipid-based drug delivery systems has recently gained focus for drugs characterized by poor aqueous solubility. The improved aqueous solubility overcomes one of the main barriers that limit their bioavailability. The objective of this work was to improve the solubility and oral bioavailability of Avanafil (AVA), a recently approved second generation type 5 phospodiesterase inhibitor used for erectile dysfunction.AVA was formulated as self-nanoemulsifying drug delivery system (SNEDDS) utilizing various oils, surfactants, and cosurfactants. The solubility of AVA in various oils, surfactants, and cosurfactants was determined. Ternary phase diagram was constructed to identify stable nanoemulsion region. The prepared AVA loaded SNEDDS were assessed for optical clarity, droplet size, conductivity, and stability studies. In vitro drug release and in vivo pharmacokinetic parameters using animal model were also investigated. Results revealed that stable AVA (SNEDDS) were successfully developed with a droplet size range of 65 to 190 nm. SNEDDS composed of 25% dill oil, 55% Tween 80, and 20% propylene glycol successfully improved solubilization of AVA (over 80% within 30 min) vis-a-vis the powder AVA (35% within 30 min). In vivo pharmacokinetic showed a significant (P < 0.05) increase in Cmax, reduction in Tmax, and SNEDDS enhanced the bioavailability in the rats by 1.4-fold when compared with pure drug.
authors.affiliation: Department of Pharmaceutics & Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Usama A
authors.initials: UA
authors.lastname: Fahmy
authors.forename: Osama A A
authors.initials: OA
authors.lastname: Ahmed
authors.forename: Khaled M
authors.initials: KM
authors.lastname: Hosny
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D045703:Emulsifying Agents / Q000737:chemistry*; D004655:Emulsions; D008297:Male; D008657:Metabolic Clearance Rate; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D044367:Phase Transition; D011743:Pyrimidines / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D045703:Emulsifying Agents; D004655:Emulsions; D053769:Nanocapsules; D011743:Pyrimidines; C553414:avanafil