Back to Journals » Drug Design, Development and Therapy » Volume 9

Custom fractional factorial designs to develop atorvastatin self-nanoemulsifying and nanosuspension delivery systems – enhancement of oral bioavailability

Authors Hashem F, Al-Sawahli M, Nasr M, Ahmed OAA

Received 5 April 2015

Accepted for publication 24 April 2015

Published 19 June 2015 Volume 2015:9 Pages 3141—3152

DOI https://doi.org/10.2147/DDDT.S86126

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Professor Shu-Feng Zhou

Fahima M Hashem,1 Majid M Al-Sawahli,2 Mohamed Nasr,1 Osama AA Ahmed3,4

1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Cairo, Egypt; 2Holding Company for Biological Products and Vaccines (VACSERA), Giza, Egypt; 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Minia University, Minia, Egypt

Abstract: Poor water solubility of a drug is a major challenge in drug delivery research and a main cause for limited bioavailability and pharmacokinetic parameters. This work aims to utilize custom fractional factorial design to assess the development of self-nanoemulsifying drug delivery systems (SNEDDS) and solid nanosuspensions (NS) in order to enhance the oral delivery of atorvastatin (ATR). According to the design, 14 experimental runs of ATR SNEDDS were formulated utilizing the highly ATR solubilizing SNEDDS components: oleic acid, Tween 80, and propylene glycol. In addition, 12 runs of NS were formulated by the antisolvent precipitation–ultrasonication method. Optimized formulations of SNEDDS and solid NS, deduced from the design, were characterized. Optimized SNEDDS formula exhibited mean globule size of 73.5 nm, zeta potential magnitude of -24.1 mV, and 13.5 µs/cm of electrical conductivity. Optimized solid NS formula exhibited mean particle size of 260.3 nm, 7.4 mV of zeta potential, and 93.2% of yield percentage. Transmission electron microscopy showed SNEDDS droplets formula as discrete spheres. The solid NS morphology showed flaky nanoparticles with irregular shapes using scanning electron microscopy. The release behavior of the optimized SNEDDS formula showed 56.78% of cumulative ATR release after 10 minutes. Solid NS formula showed lower rate of release in the first 30 minutes. Bioavailability estimation in Wistar albino rats revealed an augmentation in ATR bioavailability, relative to ATR suspension and the commercial tablets, from optimized ATR SNEDDS and NS formulations by 193.81% and 155.31%, respectively. The findings of this work showed that the optimized nanocarriers enhance the oral delivery and pharmacokinetic profile of ATR.

Keywords: nanostructures, optimization, experimental design, fractional factorial design

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Other articles by this author:

Mechanistic analysis of Zein nanoparticles/PLGA triblock in situ forming implants for glimepiride

Ahmed OAA, Zidan AS, Khayat M

International Journal of Nanomedicine 2016, 11:543-555

Published Date: 3 February 2016

Optimized zein nanospheres for improved oral bioavailability of atorvastatin

Hashem FM, Al-Sawahli MM, Nasr M, Ahmed OA

International Journal of Nanomedicine 2015, 10:4059-4069

Published Date: 19 June 2015

Evaluation of combined famotidine with quercetin for the treatment of peptic ulcer: in vivo animal study

Abourehab MA, Khaled KA, Sarhan HA, Ahmed OA

Drug Design, Development and Therapy 2015, 9:2159-2169

Published Date: 13 April 2015

Improved corneal bioavailability of ofloxacin: biodegradable microsphere-loaded ion-activated in situ gel delivery system

Sayed EG, Hussein AK, Khaled KA, Ahmed OAA

Drug Design, Development and Therapy 2015, 9:1427-1435

Published Date: 10 March 2015

Readers of this article also read:

Green synthesis of water-soluble nontoxic polymeric nanocomposites containing silver nanoparticles

Prozorova GF, Pozdnyakov AS, Kuznetsova NP, Korzhova SA, Emel’yanov AI, Ermakova TG, Fadeeva TV, Sosedova LM

International Journal of Nanomedicine 2014, 9:1883-1889

Published Date: 16 April 2014

Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

Ashwanikumar N, Kumar NA, Nair SA, Kumar GS

International Journal of Nanomedicine 2012, 7:5769-5779

Published Date: 15 November 2012

A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone

Hu Z, Liao M, Chen Y, Cai Y, Meng L, Liu Y, Lv N, Liu Z, Yuan W

International Journal of Nanomedicine 2012, 7:5719-5724

Published Date: 12 November 2012

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010