*Article* **Preparation and Characterization of Silymarin Gel: A Novel Topical Mucoadhesive Formulation for Potential Applicability in Oral Pathologies**

**Divyambika Catakapatri Venugopal 1,† , Reshma Devi Senthilnathan 2,† , Saba Maanvizhi <sup>2</sup> , Yasasve Madhavan <sup>1</sup> , Sathasivasubramanian Sankarapandian <sup>1</sup> , Vijayalakshmi Ramshankar 3,\* and Mangathayaru Kalachaveedu 4,\***


**Abstract:** *Silybum marianum* has been used for centuries by herbalists and physicians to treat different forms of liver diseases. It contains flavonoid, which has antioxidant, anti-inflammatory, antifibrotic and anticancer properties. The objective of this research was to develop a silymarin-based mucoadhesive gel for prolonged release in oral mucosa and to evaluate the same by using *in vitro* drug release kinetic models and *ex vivo* methods for drug permeation using chicken buccal mucosa. The mucoadhesive gel was formulated in different trials by varying the concentration of silymarin and polymer. Out of 10 formulation trials, the F10 optimized trial was characterized for *in vitro* physicochemical parameters such as pH, homogeneity, viscosity, stability, drug content, *in vitro* drug release, *in vitro* antioxidant assay and *ex vivo* permeation study. Trial 10 was chosen as the best trial formulation among the other trials and was marked as an optimal trial. The physicochemical properties observed were pH to be 6.4 ± 0.01, the gel free of lumps, spreadability of 23.75 ± 0.03 and drug content of 32.77 ± 0.20 mg/g. It had no physiological changes such as color shift or fluid exudate segregation after 6 months of storage at room temperature. *In vitro* drug release established the presence of a non-fickian mechanism and demonstrated dose-dependent antioxidant activity. *Ex vivo* findings indicated 21.97 ± 0.18% release, proving that the gel can permeate through the oral mucosal membrane. Our future research will concentrate on expanding the therapeutic scope by developing the formulation trial F10 to a nanoformulation and conducting clinical trials for its potential use in various oral diseases.

**Keywords:** silymarin; mucoadhesive gel; topical formulation; drug release; bioavailability
