Enhanced dissolution and intestinal absorption of adefovir dipivoxil by cocrystal formation with acetaminophen / 药学学报

ABSTRACT

In current study, adefovir dipivoxil (AD)-acetaminophen (AP) cocrystal (molar ratio, 11) was prepared by slow evaporation from acetonitrile, followed by physicochemical characterizations using differential scanning calorimetry, powder X-Ray diffraction and Fourier transform infrared spectroscopy. Molecular modeling showed that the phosphoester group of AD was connected with the amide group of AP through hydrogen bonds. In comparison to crystalline AD, the solubility and dissolution rate of AD from AD-AP cocrystal were significantly enhanced by 1.5-fold and 1.6-fold, respectively. In addition, based on the rat single-pass intestinal perfusion study, the permeabilities of AD in various intestinal sections (i.e., duodenum, jejunum, ileum and colon) were significantly improved (e.g., about 3-fold enhancement in duodenum) after cocrystallization with AP by inhibiting P-glyprotein mediated efflux of AD, which will benefit absorption in vivo and subsequent oral bioavailability of poorly permeable drug AD.