Structures and physical properties of the cocrystals of adefovir dipivoxil with dicarboxylic acids

The cocrystallization of adefovir dipivoxil (AD) with suberic acid (SUB) or succinic acid (SUC) was examined. X-ray diffraction was used to determine the structures of AD/SUB and AD/SUC cocrystals. Both cocrystals were formed via multiple hydrogen bonds between the adenine part of AD and the carboxylic acid groups of SUB or SUC. Longer SUB effectively dispersed AD molecules, and AD hydrogen-bonded only to SUB. When shorter SUC was used, AD formed hydrogen bonding with both SUC and adjacent AD. As a result, the cocrystal compositions were AD/SUB=1:1 and AD/SUC=2:1. Both cocrystals displayed superior thermal stability and increased aqueous solubility. The present study demonstrated that the adenine and similar structures of active pharmaceutical ingredients could be used to produce cocrystals of improved physical properties.