Objective: Design and optimization of starch hyaluronate as a new superdisintegrant by employing a 23factorial design in the formulation of nisoldipine fast-dissolving tablets to increase the bioavailability and patient compliance.Methods: The esterification process was used to prepare starch hyaluronate. The micromeritics and physical characteristics of starch hyaluronate were assessed, and nisoldipine fast-dissolving tablets have been formulated by a direct compression method using starch hyaluronate as a new superdisintegrating agent. In vitro dissolution, in vivo pharmacokinetics, and post-compression parameters were assessed. According to ICH requirements, optimized formulation stability tests were carried out under accelerated conditions for six months.Results: The synthesized starch hyaluronate was crystalline and tested to be insoluble in both organic and aqueous solvents. Nisoldipine fast-dissolving tablets with excellent tablet properties and enhanced drug dissolution efficiency were produced by using starch hyaluronate as a super disintegrant. NMR study confirmed that the starch and hyaluronic acid were bonded with the ester linkage. The formulation NF6, which contained crospovidone, and starch hyaluronate in a 5 percent concentration as super disintegrants, demonstrated the lowest disintegration time (11±2se) and 99.6 percent drug dissolution within 10 minutes of all the formulations (NF1 to NF8). The drug dissolution characteristics of formulation NF6 were comparable to those of formulation NF2 (92.8%), which included a 5 percent concentration of starch hyaluronate. Optimized formulation NF2 demonstrated enhanced relative bioavailability of the drug and quickly reached peak plasma levels.Conclusion: Physical properties, disintegration time, pharmacokinetic studies, and in vitro dissolution studies led researchers to the conclusion that optimized formulation was stable, achieved peak plasma concentration quickly, and had greater relative bioavailability. Hence starch hyaluronate is also recommended as a new super disintegrant in the development of fast-acting tablets of poorly soluble drugs.