Title: Sildenafil citrate nanoemulsion vs. self-nanoemulsifying delivery systems: rational development and transdermal permeation

Authors: Yosra S.R. Elnaggar, Magda A. El-Massik, Ossama Y. Abdallah

Addresses: Faculty of Pharmacy, Department of Pharmaceutics, Alexandria University, 1 Khartoum Square, Azarita, Messalla Post Office, P.O. Box 21521, Alexandria, Egypt. ' Faculty of Pharmacy and Drug Manufacturing, Department of Pharmaceutics, Pharos University, Alexandria, Egypt. ' Faculty of Pharmacy, Department of Pharmaceutics, Alexandria University, 1 Khartoum Square, Azarita, Messalla Post Office, P.O. Box 21521, Alexandria, Egypt

Abstract: Sildenafil citrate (SC) is the first choice drug for erectile dysfunction. Nevertheless, drug oral delivery is hampered by some obstacles including first pass metabolism, numerous side effects, relatively short duration and long onset of action. Furthermore, drug delivery formulation and transdermal application of SC is challenged by its amphoteric nature, low oil and water solubility, pH-dependent characteristics and poor membrane permeability. In this paper, relevance of nanomedicine to improve SC characteristics and transdermal permeation was assessed. SC-loaded self-nanoemulsifying drug delivery system (SNEDDS) and nanoemulsions have been developed and appraised. Both nanocarriers encompassed the bioactive excipient, Cremophor RH40® as a surfactant. The nanocarriers encompassed an oil blend of Caproyl 90® and Maisine 35-1® and propylene glycol as a co-surfactant. Nanocarrier assessment was based on solubility studies, robustness to dilution, globule size analysis, cloud point measurement, transmission electron microscopy and in-vitro dialysis. Transdermal permeation study of nanocarriers and drug suspensions via human skin was performed using modified Franz diffusion assembly. SC-SNEDD system was robust to dilution in different media and folds of dilution, maintaining its nano-metric range. SC-nanoemulsion exhibited spherical shaped globules 70 nm in size. Cloud points of all dispersions formed were higher enough than 37°C. In-vitro release from both nanocarriers was significantly higher than drug suspension. Nanoemulsion elaborated could significantly enhance transdermal permeation of SC with higher initial permeation and prolonged release. Paradoxically, SC-SNEDDS exhibited scanty transdermal permeation that could be attributed to low water content of stratum corneum. Nanoemulsion and SNEDDS elaborated exhibited promising in-vitro characteristics for oral sildenafil citrate delivery whereas nanoemulsion elaborated was promising for SC transdermal permeation, as well.

Keywords: sildenafil citrate; nanotechnology; SNEDDS; nanoemulsion; self-nanoemulsifying delivery; transdermal permeation; erectile dysfunction; drug delivery; nanomedicine; nanocarriers; drug suspension.

DOI: 10.1504/IJNT.2011.041443

International Journal of Nanotechnology, 2011 Vol.8 No.8/9, pp.749 - 763

Published online: 22 Jul 2011 *

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