Joint action of pharmaceuticals in model lipid membranes: calorimetric effects

Joint action of a number of pharmaceuticals has been studied in multibilayer model membranes of L-α-dipalmitoylphosphatidylcholine. Shift of the main phase transition temperature of the membrane under the pharmaceuticals introduction (∆Tm) was determined by means of differential scanning calorimetry and used as a basic factor of their membranotropic action (MA). Pairs of pharmaceuticals were selected with various character of lipophylicity and MA; cholesterol was used as the membrane compound with the well-known MA. Revelation and identification of the effects of joint action was performed by comparison of ∆Tm values under separate and joint introduction of the pharmaceuticals. Effects of joint action appear similar for hydrophobic azithromycin and hydrophilic succinylcholine in their combinations both with povidone and with cholesterol. Examination of joint action of an active pharmaceutical intgredient (API) and and an excipient allowed us to establish a certain advantage of the API's MA in the pairs azithromycin-lactose and azithromycin-dimetylsulfoxide, and additivity of the MA in the pair amixin-hypromelose.