Drug-drug　cocrystals,　which　can　regulate　physicochemical　properties　of　individual　drugs　and　might　produce　synergistic　therapeutic　effects,　have　drawn　growing　interest　in　the　pharmaceutical　industry.　In　this　study,　a　novel　drug-drug　(1:1)　cocrystal　hydrate　of　slightly　water-soluble　dihydromyricetin　(DMY)　and　highly　water-　soluble　pentoxifylline　(PTX),　DMY-　PTX　center　dot　H2O　(1),　was　prepared　by　a　slurry　method.　The　single-crystal　X-ray　diffraction　results　reveal　that　the　cocrystal　is　formed　through　hydrogen-bonding　interactions　between　hydroxyl　groups　of　DMY　and　four　acceptors　of　PTX.　The　dynamic　vapour　sorption　results　indicate　that　the　cocrystal　displays　reduced　hydrophilicity　compared　with　DMY.　It　is　found　that　cocrystal　formation　narrows　the　solubility　difference　between　two　parent　drugs.　The　equilibrium　solubility　of　PTX　decreases　greatly,　while　that　of　DMY　increases　slightly.　As　a　result,　DMY　and　PTX　are　synchronously　and　sustainedly　released　from　the　cocrystal.　Further,　a　synergistic　anti-cancer　effect　of　the　cocrystal　DMY-PTX　center　dot　H2O　(1)　on　HepG2　cells　in　vitro　at　a　drug　concentration　of　100　mu　M　was　discovered.　This　study　brings　evidence　of　cocrystallization　as　a　successful　approach　for　synchronous　sustained-release　of　two　drugs　with　substantially　different　aqueous　solubility.　(C)　2021　American　Pharmacists　Association.　Published　by　Elsevier　Inc.　All　rights　reserved.