Molecular simulation of ibuprofen passing across POPC membrane

Permeability assessment is an important procedure in the drug development process, and drug partitioning in membrane bilayer is related to permeability. To investigate the pH dependence on drug partitioning, the process of different ionization state of ibuprofen passing across POPC bilayer was studied using molecular dynamics simulation. The results show that both atomic charge scheme and ionization state of the drug affect the value and shape of energy profile when passing across the POPC bilayer. The neutral ibuprofen (ibuprofen under acidic condition) has a much lower energy barrier as compared with the anionic ibuprofen (ibuprofen under basic condition). Meantime, hydrogen bond analysis also certifies that it is easy for neutral ibuprofen to pass from bulk water to bilayer center. Our calculation suggests that the ionization state of ibuprofen may be changed between neutral and anionic state when passing across membrane: it may be ionized outside the membrane and neutralized inside the membrane.