Controlled release formations of drugs were prepared from bichalcophene derivatives as drugs and sodium carboxymethylcellulose (NaCMC) as a matrix of natural polysaccharide. The release behavior of bichalcophene derivatives from the NaCMC matrix was studied. The solubility and chemical nature of these derivatives have a significant effect on their release characteristics. The current study showed that the cationic amidinic bichalcophene derivatives exhibit a slow release rate due to the formation of hydrogen bonds between their positively charged amino groups and the negatively charged carboxyl groups of the polymer matrix. The derivatives of poor solubility exhibit a slow release rate while soluble derivatives show a fast release rate