The effects of two binders povidone and copovidone aqueous solution on the quality and properties of penicillin V potassium tablets were compared. The compatibility of povidone K29/30 and plasdone S 630 with penicillin V potassium was studied. The 10% ethanol aqueous solution of these two excipients was selected as the binder, and the penicillin V potassium tablets were prepared by wet granulation. The effects of two kinds of excipients on the quality and properties of penicillin V potassium tablets were compared by investigating the compatibility of API and the two auxiliary materials, the friability, the disintegration time and the rapid stability of the tablets. The results show that plasdone S630 has good hydrophobic properties, which can improve the impurity growth problem caused by high humidity, and the tablets prepared by plasdone S630 adhesive have better fragility.