After HIV, tuberculosis (TB) is the world's second most frequent disease. MTB (Mycobacterium tuberculosis) is a major infectious disease that poses a considerable public health issue. Fixed-dose drug combination microspheres appear to be a better option for long-term, regulated medication therapy. The drugs could be given orally once a week to encourage patient compliance. For long-term pharmaceutical therapy, fixed-dose drug combination microspheres appear to be a superior option. Oral administration is the most common and favored mode of pharmaceutical administration. Drug release is modulated throughout the GI tract with oral controlled-release (CR) formulations. Swelling and expanding systems, floating systems, forms of the mucoadhesive systems of high-density dose, and magnetic systems have all been employed. The goal of this study is to develop rifampicin-floating microspheres that will increase gastric retention time. The influence of quercetin on in-vitro drug release has been looked. The efficiency of entrapment was determined to be 76.50 percent. After 8 hours, the percentage buoyancy was observed at 61.50. In gastric media, the microspheres produced displayed extended drug release, indicating that they could be employed for long-term anti-tubercular medicine delivery.