Incorporating valsartan in sesame oil enriched self-nanoemulsifying system-loaded liquisolid tablets to improve its bioavailability

Khalid M El-Say; Sami H Alamri; Helal H Alsulimani; Waleed S Alharbi; Abdelsattar M Omar; Martin K Safo; Tarek A Ahmed

doi:10.1016/j.ijpharm.2023.122966

Incorporating valsartan in sesame oil enriched self-nanoemulsifying system-loaded liquisolid tablets to improve its bioavailability

Int J Pharm. 2023 May 25:639:122966. doi: 10.1016/j.ijpharm.2023.122966. Epub 2023 Apr 20.

Authors

Khalid M El-Say¹, Sami H Alamri², Helal H Alsulimani³, Waleed S Alharbi⁴, Abdelsattar M Omar⁵, Martin K Safo⁶, Tarek A Ahmed⁷

Affiliations

¹ Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Electronic address: kelsay1@kau.edu.sa.
² Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Electronic address: smarzouqalamri@stu.kau.edu.sa.
³ Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Electronic address: halsulimani@kau.edu.sa.
⁴ Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Electronic address: wsmalharbi@kau.edu.sa.
⁵ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Electronic address: asmansour@kau.edu.sa.
⁶ Department of Medicinal Chemistry, and the Institute for Structural Biology, Drug Discovery, and Development, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA. Electronic address: msafo@vcu.edu.
⁷ Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Electronic address: tabdelnapy@kau.edu.sa.

PMID: 37084835
DOI: 10.1016/j.ijpharm.2023.122966

Abstract

Valsartan (VST) is a poorly soluble antihypertensive drug characterized by its limited dissolution rate and low bioavailability. This study aims to improve VST solubility and dissolution rate via developing liquisolid tablets (LSTs) containing a self-nanoemulsifying drug delivery system (SNEDDS), which is expected to enhance VST bioavailability. This aim was achieved via two designs of experiment. The first was the simplex-lattice design to optimize VST-loaded-SNEDDS using sesame oil, Tween 80, and polyethylene glycol 400. The second was the 3²-3-level factorial design to optimize the liquisolid system using the SNEDDS-loaded VST and Neusilin®US2 as a carrier and fumed silica as a coating material. Different excipient ratios (X₁) and varioussuper-disintegrants (X₂) were also used in developing the optimized VST-LSTs. Thein vitrodissolution of VST from LSTs was compared with the marketed product (Diovan®). Non-compartmental analysis of plasma data after extravascular input with the linear trapezoidal method was used to calculate thepharmacokinetic parameters of the optimized VST-LSTs compared with the marketed tablet in male Wistar rats. The optimized SNEDDS compromised 24.9% sesame oil, 33.3% surfactant, and 41.8% cosurfactant, giving 173.9 nm size and 63.9 mg/ml loading capacity. Also, the SNEDDS-loaded VST tablet revealed good quality attributes with the release of 75% of its content in 5 min and 100% within 15 min. On the other hand, the marketed product took 1 h for the entire drug to be released.Moreover, the maximum plasma concentration (C_max) of the optimizedVST-LSTwas6585.33 ng/ml within 1 h (T_max), compared to 2884.67 ng/ml within 2 h of the marketed tablet.The relative bioavailability of the SNEDDS-loaded VST tablet was 213.7% compared to that of the marketed tablet, indicating that this formulation approach could be applied for increasing solubility, dissolution behavior in GIT, and bioavailability of poorly water-soluble drugs.

Keywords: Bioavailability; Industrial development; Liquisolid technique; SNEDDS; Valsartan.

MeSH terms

Animals
Biological Availability
Drug Delivery Systems / methods
Emulsions
Excipients
Male
Nanoparticles*
Rats
Rats, Wistar
Sesame Oil*
Solubility
Tablets
Valsartan

Substances

Valsartan
Sesame Oil
Emulsions
Excipients
Tablets