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

Hibah M Aldawsari,Osama A A Ahmed,Usama A Fahmy,Fathy Abd-Allah

doi:10.3390/pharmaceutics12060596

Hibah M Aldawsari, Osama A A Ahmed + Show 2 more

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https://doi.org/10.3390/pharmaceutics12060596

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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.

Highlights

Avanafil (AVA, Figure 1) is a drug recently approved in the United States and Europe [1,2]
AVA showed a more favorable profile against other enzymes known to be affected by this class of drugs, especially PDE6, where AVA was more than 100 times less potent than the PDE5
Lactide:glycolide (50:50), mol wt 30,000–60,000, DCM, polyvinyl alcohol (PVA) Mw 89,000–98,000 and all other chemicals were from Sigma-Aldrich

Summary

Introduction

Avanafil (AVA, Figure 1) is a drug recently approved in the United States and Europe [1,2]. AVA is a second-generation phosphodiesterase type 5 inhibitor (PDI5) used for erectile dysfunction [3,4]. AVA is characterized by its faster onset and improved selectivity compared with other PDI-class drugs. AVA showed a more favorable profile against other enzymes known to be affected by this class of drugs, especially PDE6, where AVA was more than 100 times less potent than the PDE5. AVA had a low propensity for visual disturbances [1,2,5,6,7]. AVA displayed higher selectivity for PDE5 versus

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