A novel in vitro approach to investigate the effect of food intake on release profile of valsartan in solid dispersion-floating gel in-situ delivery system

• Published in: European journal of pharmaceutical sciences 2022-01, Vol.168, p.106057-106057, Article 106057
• Main Authors: Himawan, Achmad, Djide, Nana Juniarti Natsir, Mardikasari, Sandra Aulia, Utami, Rifka Nurul, Arjuna, Andi, Donnelly, Ryan.F., Permana, Andi Dian
• Format: Article
• Language: English
• Subjects: Animals; Biological Availability; Controlled release; Delayed-Action Preparations; Eating; Floating gel in situ system; Gels; Solid dispersion; Solubility; Tablets; Valsartan
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2021.106057

•Valsartan was formulated into solid dispersion which was incorporated into floating gel in-situ delivery system.•The formulations showed desirable characteristics and sustained release profiles.•The food intake did not affect the in vitro release of valsartan after 2 h in an empty gastric environment. Valsartan (VAL) is a BCS class II drug with low solubility and high permeability and, thus, its formulations often encounter low bioavailability problems. Its low bioavailability can be improved through enhanced formulation, such as incorporating it into a solid dispersion system (SD). The absorption can be further enhanced through gastroretentive systems. Herein, we developed a novel combination delivery approach consisting of floating in-situ gel and SD. VAL was incorporated with polymer carrier PVP and PEG 6000 and its solubility was then evaluated. The study found that VAL-SD containing PVP K-30 as the carrier with drug:PVP K-30 ratio of 1:3 shown highest solubility in different media. Moreover, DSC and XRD evaluations exhibited the change of VAL from crystal to amorphous following SD formulation. The SD was then formulated into floating in-situ gel preparations using sodium alginate as gel forming compound and HPMC as the controlled release matrix. The prepared VAL-SD floating in-situ gels were evaluated for their physical properties and drug release profile. The results showed that all physical evaluation of the floating in-situ gel formula possessed desirable physical properties and the use of HPMC in floating in-situ gel was able to sustain the in vitro release of VAL for 24 h in biorelevant media. Importantly, the effect of food intake on VAL release was also investigated, for the first time, showing that the VAL release could be controlled in FaSSGF (Fasted-State Simulated Gastric Fluid) in 2 h and FeSSGF (Fed-State Simulated Gastric Fluid) onwards. Thus, in can be hypothesized that the food intake did not affect the VAL release after 2 h in an empty gastric environment. Leading on from these results, in vivo studies in an animal model should be carried out to further assess the potency of this system. [Display omitted]