This study describes the integration of Quality by Design (QbD) principles in the formulation and development of topical delivery systems represents a significant advancement in pharmaceutical sciences, particularly for enhancing the efficacy and safety of active ingredients. This study applies Quality by Design (QbD) principles to develop a nanosponges gel system incorporating Berberine. Nanosponges enhance drug stability, control release, and improve skin permeation. Using Design of Experiments (DoE), key formulation parameters such as polymer concentration, surfactant type, and drug load were optimized. The gel was tested for particle size, zeta potential, drug entrapment, and release profiles, with stability and efficacy assessed in real-world conditions. A double beam UV visible spectrophotometer (Shimadzu-1700) was utilized to ascertain a substance\u27s lambda max, or absorption maxima. The lambda max of the Berberine was found to be 355.0 nm. The Berberine pH of 6.6 was discovered to be well within the parameters of the medication\u27s specification. The optimized formulations yielded an average particle size of 181.04 nm. The optimized nanosponges formulation\u27s zeta potential values (-29.0 mV) showed that the nanosponges were stable. The prepared optimized nanosponges possess high drug entrapment efficiency and found to be in the range of 90.18%. The QbD approach successfully produced a stable, efficient formulation, demonstrating its value in advancing topical drug development
