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

by Selleckchem | May 12 2023

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 63.9mg/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 1h for the entire drug to be released.Moreover, the maximum plasma concentration (Cmax) of the optimizedVST-LSTwas6585.33 ng/ml within 1h (Tmax), compared to 2884.67 ng/ml within 2h 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.

Comments：

This study aimed to improve the solubility and dissolution rate of the poorly soluble antihypertensive drug, Valsartan (VST), using liquisolid tablets (LSTs) containing a self-nanoemulsifying drug delivery system (SNEDDS). Two designs of experiment were used, the simplex-lattice design to optimize VST-loaded-SNEDDS and the 32-3-level factorial design to optimize the liquisolid system. Different excipient ratios and super-disintegrants were used in developing the optimized VST-LSTs. The optimized SNEDDS contained 24.9% sesame oil, 33.3% surfactant, and 41.8% cosurfactant, giving 173.9 nm size and 63.9mg/ml loading capacity. The SNEDDS-loaded VST tablet showed good quality attributes with the release of 75% of its content in 5 min and 100% within 15 min, compared to 1h for the marketed product to release the entire drug. The optimized VST-LSTs showed a maximum plasma concentration (Cmax) of 6585.33 ng/ml within 1h (Tmax), compared to 2884.67 ng/ml within 2h for 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 to increase the solubility, dissolution behavior in the gastrointestinal tract (GIT), and bioavailability of poorly water-soluble drugs.