Intranasal Niosomal In Situ Gel as a Promising Approach for Enhancing Flibanserin Bioavailability and Brain Delivery: In Vitro Optimization and Ex Vivo/In Vivo Evaluation
Usama A. Fahmy,
Shaimaa M. Badr-Eldin,
Osama A. A. Ahmed,
Hibah M. Aldawsari,
Singkome Tima,
Hani Z. Asfour,
Mohammed W. Al-Rabia,
Aya A. Negm,
Muhammad H. Sultan,
Osama A. A. Madkhali,
Nabil A. Alhakamy
Affiliations
Usama A. Fahmy
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Shaimaa M. Badr-Eldin
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Osama A. A. Ahmed
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Hibah M. Aldawsari
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Singkome Tima
Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
Hani Z. Asfour
Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Mohammed W. Al-Rabia
Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Aya A. Negm
Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44518, Egypt
Muhammad H. Sultan
Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia
Osama A. A. Madkhali
Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia
Nabil A. Alhakamy
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Flibanserin (FLB) is a multifunctional serotonergic agent that was recently approved by the FDA for the oral treatment of premenopausal women with hypoactive sexual desire disorder. FLB is a centrally acting drug that has a low oral bioavailability of 33% owing to its exposure to the hepatic first-pass effect, as well as its pH-dependent solubility, which could be an obstacle hindering the drug dissolution and absorption via mucosal barriers. Thus, this work aimed at overcoming the aforementioned drawbacks and promoting the nose-to-brain delivery of FLB via the formulation of an intra-nasal in situ niosomal gel. The Box–Behnken design was employed to study the impact of Span® 85 concentration (X1), hydration time (X2), and pH of the hydrating buffer (X3) on the vesicle size and drug entrapment. The optimized formulation exhibited a spherical shape with a vesicular size of 46.35 nm and entrapment efficiency of 92.48%. The optimized FLB niosomes integrated into gellan gum-based in situ gel exhibited enhanced ex vivo permeation and improved plasma and brain concentrations after nasal administration in rats compared to raw FLB. These findings highlight the capability of the proposed intra-nasal FLB niosomal in situ gel to boost the drug bioavailability and to promote its direct delivery to the brain.
