Nucleotides as new co-formers in co-amorphous systems: Enhanced dissolution rate, water solubility and physical stability

Developing co-amorphous systems is an attractive strategy to improve the dissolution rate of poorly water-soluble drugs. Various co-formers have been investigated. However, previous studies revealed that it is a challenge to develop satisfied acidic co-formers, e.g., acidic amino acids showed much poorer co-former properties than neutral and basic amino acids. Only a few acidic co-formers have been reported, such as aspartic acid , glutamic acid , and some other organic acids . Thus, this study aims to explore the possibility of adenosine monophosphate and adenosine diphosphate used as acidic co-formers. Mebendazole, celecoxib and tadalafil were used as the model drugs. The drug-co-former co-amorphous systems were prepared via ball milling and confirmed using XRPD. The dissolution study suggested that the solubility and dissolution rate of the drug-co-formers systems were increased significantly compared to the corresponding crystalline and amorphous drugs. The stability study revealed that using the two nucleotides as co-formers enhanced the physical stability of pure amorphous drugs. Molecular interactions were observed in MEB-co-former and TAD-co-former systems and positively affected the pharmaceutical performance of the investigated co-amorphous systems. In conclusion, the two nucleotides could be promising potential acidic co-formers for co-amorphous systems.