Effects of different combinations of nanocrystallization technologies on avanafil nanoparticles: in vitro, in vivo and stability evaluation

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• 作者：Kareem AbuBakr Soliman ; ^{karim.mohamed@pharma.cu.edu.eg} ; Howida Kamal Ibrahim ; Mahmoud Mohammed Ghorab
• 关键词：ANOVA ; analysis of variance ; AUC(0&minus ; &infin ; ) ; area under plasma concentration-time curve extrapolated to infinity ; Cmax ; peak plasma concentration ; D.E.(0&ndash ; 30) ; dissolution efficiency (0&ndash ; 30&thinsp ; min) ; DMSO ; dimethyl sulphoxide ; DSC ; differential scanning calorimetry ; FDA ; United States Food and Drug Administration ; HPH ; high pressure homogenization ; HLB ; hydrophilic-lipophilic balance ; HPLC ; high-performance liquid chromatography ; PDE5 ; phosphodiesterase enzyme type 5 ; PDI ; pol
• 刊名：International Journal of Pharmaceutics
• 出版年：2017
• 出版时间：30 January 2017
• 年：2017
• 卷：517
• 期：1-2
• 页码：148-156
• 全文大小：1531 K
• 卷排序：517

文摘

The study investigated the effects of different combined top-down and bottom-up nanocrystallization technologies on particle size and solid state of avanafil nanoparticles. Combined antisolvent precipitation-ultrasonication (sonoprecipitation) technique was adopted to prepare 18 formulas according to 32.21 factorial design using 3 stabilizers; Tween 80, polyvinyl alcohol (PVA) and Pluronic F68 at different concentrations with different cryoprotectants. Particle size analysis of the lyophilized formulas showed that Tween 80 was an effective nanoparticles stabilizer in contrast to Pluronic F68 and PVA which failed to prevent nanoparticles flocculation when they were used at high concentration. The combined effects of nanonization and amorphism contributed to the improvement in solubility. Further processing of the sonoprecipitated formulas by high pressure homogenization (HPH) (modified NANOEDGE™ technology) resulted in further size reduction of PVA-stabilized particles, while it stimulated flocculation of Tween-stabilized nanoparticles. Nevertheless, all of the homogenized formulas partially retrieved their crystallinity which reduced their solubility. Non-homogenized formula 2E composed of 1:2 (avanafil: Tween) with glucose as cryoprotectant, exhibited 13.68- and 2.59-fold improvement in solubility and in vitro dissolution, respectively. This formula had oral bioavailability of 137.02% relative to Spedra® tablets and it maintained its nanosize, amorphism and dissolution behavior over 6 months of storage under stress conditions.