Structure, Solubility, and Stability Analysis of Acipimox‐Theophylline Dihydrate Cocrystal

ABSTRACT Acipimox is a broad‐spectrum long‐acting lipid‐lowering agent used to treat a variety of primary and secondary hyperlipidemia. However, the poor solubility of acipimox limits its bioavailability. To improve its solubility, acipimox‐theophylline dihydrate cocrystal ( ATH ) is prepared by the traditional solvent evaporation crystallization technique for the first time. ATH is characterized by SEM, Raman, Thermal analysis, and X‐ray diffraction. Crystal structure analysis manifests that in ATH , acipimox, theophylline, and two molecules of water interact and pack to form a stable 1D tubular structure primarily through hydrogen bonding. The solubility of ATH in water, 0.1 mol/L hydrochloric acid solution, and phosphate buffer solution (pH = 7.4) is more than four times that of acipimox, indicating that the solubility of ATH is superior to that of acipimox. Moreover, ATH is more stable than acipimox in solution (298 K), light (4500 LX), high temperature (333 K), and high humidity (92.5%). Favorable solubility and stability of ATH may provide new potential for practical applications.