Azithromycin has a low water solubility; Hence, dissolution represents a rate-limiting process. The goal of the present investigation is to improve azithromycin dissolution and solubility rate. The purpose of this study was to create, characterize, and test the dissolving characteristics of an Azithromycin solid dispersion with skimmed milk. Formulated tablet of optimized batch compared with marketed formulation and study its drug release and make a formulation that gives the highest rate of solubility. This experiment was conducted utilizing the solid dispersion method. The rationale for solid dispersion is that it produces better results than other methods while costing less. Skimmed milk is used as a carrier to increase the solubility of azithromycin. Azithromycin purity is certified using assessment tests such as HPLC assay, UV spectroscopy, FTIR, and DSC. Azithromycin solid dispersion (Azithromycin in skimmed milk) SD2 consistently performs well in all physiochemical tests as compared to all batches. The designed tablet F2 batch releases the drug more effectively than the marketed one. Azithromycin’s solubility was successfully enhanced by utilizing the solid dispersion method with skimmed milk. Batch SD 2 gives the highest results in all parameters like solubility. Preformulation study, mainly in tablet formulation, also it gives the highest solubility.