High-pressure Polymorphism in Lamivudine

•The polymorphic transformation of lamivudine under high pressure.•The lamivudine sample underwent two phase transitions at 1.26 GPa and 7.23 GPa.•Phase transitions of lamivudine were inconsistent with the conformational changes.•High pressure-induced polymorphic transformations of lamivudine were reversible. This work is devoted to the effect of pressure on the structure of lamivudine by using Raman and infrared spectroscopy in diamond anvil cells. The results showed a transition from tetragonal crystal Form Ⅱ to an unknown Form Ⅲ' at approximately 1.26 GPa, followed by a transition from Form Ⅲ' to Form Ⅳ' at pressure of 7.23 GPa. The phase transitions were marked by unique profiles and pressure-dependent characteristic modes. Pressure-induced changes in structural symmetry led to conformational transition in lamivudine. Furthermore, there was a considerable conformational variation between A and D in lamivudine molecule to maintain structural balance. Spectroscopic measurements indicated that these pressure-induced changes were reversible below approximately 0.1 GPa.