Vilazodone-phospholipid mixed micelles for enhancing oral bioavailability and reducing pharmacokinetic variability between fed and fasted states.

Autor: El Said HS; Faculty of Pharmacy, MSA University, 26 July Mehwar Road, 6(th) October City 12451, Egypt; Biomaterials, Bio-engineering and Nanomedicine (BioN) Lab, Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, White Swan Road, Portsmouth PO1 2DT, UK., Lalatsa A; Biomaterials, Bio-engineering and Nanomedicine (BioN) Lab, Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, White Swan Road, Portsmouth PO1 2DT, UK; Strathclyde Institute of Pharmacy and Biomedical Sciences, John Arbuthnot Building, 161 Cathedral Street, Glasgow G4 0RE, UK., Al-Mahallawi AM; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt. Electronic address: Abdulaziz.mohsen@pharma.cu.edu.eg., Saddar El Leithy E; Faculty of Pharmacy, MSA University, 26 July Mehwar Road, 6(th) October City 12451, Egypt; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt., Ghorab DM; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2022 Sep 25; Vol. 625, pp. 122080. Date of Electronic Publication: 2022 Aug 03.
DOI: 10.1016/j.ijpharm.2022.122080
Abstrakt: Despite the effectiveness and high tolerability of vilazodone (VLZ) as an antidepressant, its use is still limited due to its poor solubility and food dependent absorption. This study aims to load VLZ-phospholipid complex into self-assembled micelles forming VLZ-PL mixed micelles (VLZ-PL-MM), that can enhance VLZ solubility, improve its bioavailability and reduce the pharmacokinetic variability between the fed and fasting conditions. The effect of surfactant type and concentration was assessed using four different non-ionic surfactants (Brij 58, Tween 80, Labrasol and Pluronic F127) in four different weight ratios between the drug-complex and surfactant (1:0.5, 1:1, 1:2 and 1:3 w/w). Two VLZ-PL-MM formulae prepared using Brij 58 and Labrasol in 1:3 w/w ratio were selected as optimised ones since they have the highest encapsulation efficiency (100.83 and 93.87%, respectively), a particle size below 250 nm (206.73 and 221.33 nm, respectively) and negative zeta potential values (-29.63, -17.20 mV, respectively). Lyophilisation of these formulations using 3% sucrose was successful with no statistical changes in particle size and zeta potential upon rehydration. Both formulations elicited faster and higher in-vitro drug release profiles compared to the pure drug and the marketed tablet. In addition, both selected formulae improved ex-vivo permeation across rabbit intestinal membrane compared to the pure drug and the marketed tablet, with marked superiority of the one prepared using Brij 58. The results of the in-vivo study in male albino rabbits revealed similar AUC 0-24 values after the oral administration of the best achieved VLZ-PL-MM system under fed and fasted conditions (769.89 and 741.55 ng.h mL -1 , respectively). On the other hand, the marketed product showed significantly lower values of the AUC 0-24 relative to the VLZ-PL-MM system and there was a marked enhancement of absorption of drug from the marketed product in presence of food (244.24 and 174.96 ng.h mL -1 under fed and fasted conditions, respectively). In addition, VLZ concentrations in the brain after 24 h obtained from the selected VLZ-PL-MM were significantly higher than those obtained from marketed tablet under fed and fasted conditions. Thus, the phospholipid mixed micelles formulation enhances the oral bioavailability of the poorly soluble drug and reduces the pharmacokinetic variability between fasting and fed conditions.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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