One-Step Synthesis of a Drug-Drug Cocrystal Hydrate Using Hot Melt Extrusion

Hot melt extrusion (HME) has been proven to be a viable technology for the synthesis of pharmaceutical cocrystals of high quality in a continuous manner. In this study, we investigated the development process for producing drug-drug cocrystals that can be used as fixed-dose combination products to reduce the tablet size. The coprocessing of two drug substances for the formation of extruded lamivudine-zidovudine hydrate cocrystal was fully optimized. The effect of critical processing parameters such as screw configuration and temperature profiles ranging from 75 to 115 degrees C, including the water amounts, on the drug-drug cocrystal quality was evaluated. The synthesized lamivudine-zidovudine hydrate cocrystals presented high purity at 98% and superior flow (free-flowing powder, FF = 10.97) compared to the physical mixture (cohesive, FF = 2.31), but there was no change to the intrinsic dissolution in comparison to the parent drug substances. No cocrystal dissociation was observed in storage stability studies. Finally, a fully HME continuous process without including a drying step for the synthesis of a drug-drug cocrystal hydrate was designed.