Formulation Development and Comprehensive <i>In Vitro</i> Evaluation of Silymarin-Integrated Isoniazid Tablets for Potential Therapeutic Efficacy in Tuberculosis Treatment

Isoniazid (INH) is a cornerstone due to its potent bactericidal activity against Mycobacterium tuberculosis. However, its extended use is frequently associated with hepatotoxicity, a severe side effect that can lead to discontinuation of therapy and compromise treatment outcomes. INH-induced hepatotoxicity is primarily attributed to the generation of reactive metabolites that cause oxidative stress and hepatocyte damage. Silymarin, derived from the seeds of Silybum marianum, is a well-known natural hepatoprotective agent. This makes it a promising candidate for mitigating drug-induced liver injuries, including those caused by INH. This study aimed to develop and evaluate a novel combination tablet of silymarin and isoniazid, formulated using the direct compression method. The combination tablets were subjected to a comprehensive evaluation encompassing physicochemical properties, in vitro drug release studies, stability testing, and preclinical efficacy assessments. The optimized formulation, designated as F3, demonstrated desirable mechanical and release characteristics, with a hardness of 5.8 kg/cm² and friability of 0.4%. In vitro release studies revealed rapid release of isoniazid, achieving 96.5% within the first hour, ensuring effective anti-mycobacterial action. Concurrently, silymarin was released in a sustained manner over 8 hours, providing prolonged hepatoprotective effects. In conclusion, the novel silymarin-isoniazid combination tablet offers a dual advantage of effective anti-TB therapy and substantial hepatoprotection. This formulation represents a significant advancement in TB treatment strategies, with the potential to enhance patient adherence and treatment outcomes by mitigating INH-induced hepatotoxicity. The drug content remaining at 98.96% and no change in dissolution behavior.