Thermodynamic and kinetic investigation on the crucial factors affecting adefovir dipivoxil-saccharin cocrystallization.

Purpose: The aim of this study was to perform a thermodynamic and kinetic investigation on the crucial factors affecting the cocrystallization between adefovir dipivoxil (AD) and saccharin (SAC).

Methods: Phase solubility diagrams and ternary phase diagrams were constructed based on the solubility data of AD, SAC and their cocrystals in ethanol, isopropanol and ethyl acetate at different temperatures. The conductimetric method was used to determine the induction time.

Coformer selection based on degradation pathway of drugs: a case study of adefovir dipivoxil-saccharin and adefovir dipivoxil-nicotinamide cocrystals.

Adefovir dipivoxil (AD) is a bis(pivaloyloxymethyl) prodrug of adefovir with chemical stability problem. It undergoes two degradation pathways including hydrolysis and dimerization during storage. Pharmaceutical cocrystallization exhibits a promising approach to enhance aqueous solubility as well as physicochemical stability.