Abacavir
(ABC) is a carbocyclic 2′-deoxyguanosine nucleoside
reverse transcriptase inhibitor specifically prescribed for the treatment
of HIV infection. However, as a BCS class III drug, the poor permeability
seriously limits its absorption in the body. This study attempts to
improve the permeability of ABC through the crystal engineering method
of salt/cocrystal formation. Herein, four multicomponent crystals
of ABC with dicarboxylic acids were prepared: namely, the salt ABC-oxalic
acid (ABC-OXA) and the cocrystals ABC-glutaric acid (ABC-GLA), ABC-suberic
acid (ABC-SUA), and ABC-azelaic acid (ABC-AZA). The salt/cocrystals
were characterized by single-crystal X-ray diffraction (SCXRD), powder
X-ray diffraction (PXRD), differential scanning calorimetry (DSC),
and Fourier transform infrared (FT-IR) spectroscopy. In comparison
with ABC, the synthesized salt/cocrystals showed significant improvement
in the aqueous solubility, dissolution rate, and permeability. In
addition, a correlation of permeability revealed that the permeability
of abacavir and its salt and cocrystals was mainly determined by the
concentration gradient in the donor chamber and influenced by multiple
factors, including the partition coefficient (lipophilicity). This
study is another successful example of improving the solubility and
permeability of drugs through crystal engineering of salt and cocrystal
formation.