Development and Evaluation of Avanafil Self-nanoemulsifying Drug Delivery System with Rapid Onset of Action and Enhanced Bioavailability

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• 作者：Usama A. Fahmy ; Osama A. A. Ahmed ; Khaled M. Hosny
• 关键词：avanafil ; erectile dysfunction ; dill oil ; self ; nanoemulsifying ; SNEDDS
• 刊名：AAPS PharmSciTech
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：16
• 期：1
• 页码：53-58
• 全文大小：411 KB
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• 刊物主题：Pharmacology/Toxicology; Biotechnology; Biochemistry, general; Pharmacy;
• 出版者：Springer US
• ISSN：1530-9932

文摘

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--.05) increase in Cmax, reduction in Tmax, and SNEDDS enhanced the bioavailability in the rats by 1.4-fold when compared with pure drug.