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Optimized Nanostructured Lipid Carriers Integrated into In Situ Nasal Gel for Enhancing Brain Delivery of Flibanserin

Authors Fahmy UA, Ahmed OAA, Badr-Eldin SM, Aldawsari HM, Okbazghi SZ, Awan ZA, Bakhrebah MA, Alomary MN, Abdulaal WH, Medina C, Alhakamy NA

Received 25 April 2020

Accepted for publication 4 July 2020

Published 24 July 2020 Volume 2020:15 Pages 5253—5264


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Thomas J. Webster

Usama A Fahmy,1 Osama AA Ahmed,1 Shaimaa M Badr-Eldin,1,2 Hibah M Aldawsari,1 Solomon Z Okbazghi,3 Zuhier A Awan,4 Muhammed A Bakhrebah,5 Mohammad N Alomary,5 Wesam H Abdulaal,6 Carlos Medina,7 Nabil A Alhakamy1

1Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 3Global Analytical and Pharmaceutical Development, Alexion Pharmaceuticals, New Haven, Connecticut, NE 06510, USA; 4Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 5Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh 11442, Kingdom of Saudi Arabia; 6Department of Biochemistry, Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; 7School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin Ireland

Correspondence: Shaimaa M Badr-Eldin Email

Background and Aim: Flibanserin (FLB) is a multifunctional serotonergic agent used for treating hypoactive sexual desire disorder in premenopausal women via oral administration. FLB has a reported limited oral bioavailability of 33% that could be attributed to the drug’s first-pass metabolism. In addition, FLB has a pH-dependent solubility that could be a challenging factor for drug dissolution in the body neutral fluid, and consequently, absorption via mucosal barriers. Thus, this work aims at investigating the potential of utilizing nanostructured lipid carriers (NLCs) to overcome the aforementioned drawbacks and to enhance nose-to-brain drug delivery.
Methods: Box-Behnken design was applied to explore the impact of solid lipid % (SL%, X1), liquid lipid % (LL%, X2), and sonication time (ST, X3) on particle size. The optimized NLC formulation was characterized and incorporated into gellan gum in situ gel. The prepared gel was subjected to in vitro drug release, in vivo pharmacokinetic performance, and histopathological assessment in rats.
Results: Statistical analysis revealed a significant negative effect for both SL% and ST on NLCs size. In contrast, a significant positive effect was observed for the LL%. The optimized formulation showed spherical shape with vesicular size of 114.63 nm. The optimized FLB-NLC in situ gel exhibited adequate stability and enhanced in vitro release compared to raw FLB control gel. The plasma and brain concentrations of the drug after nasal administration in rats increased by more than 3– 6-fold, respectively, compared to raw FLB in situ gel. In addition, the histopathological studies revealed the absence of any pathological signs.
Conclusion: The aforementioned results highlight the safety of FLB-NLC in situ nasal gel and its potential to improve the drug bioavailability and brain delivery.

Keywords: flibanserin, nanostructured lipid carrier, Compritol® 888 ATO, almond oil, gellan gum, pharmacokinetics

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