Hydrolysis and stability of acetylsalicylic acid in stearylamine-containing liposomes.
The hydrolysis and the stabilization of acetylsalicylic acid (ASA) in liposomes at 30 degrees C were studied. The liposomes consisted of dimyristoylphosphatidylcholine (DMPC) and stearylamine. At pH 4.0 and 8.0, the pseudo-first-order rate constants (kobs) in DMPC: stearylamine (2: 1 mole ratio) liposomes were approximately 60% of the values in control solutions (kB) if ASA was incorporated via the organic phase. In contrast, when ASA was added via the aqueous phase, kobs = kB at pH 4.0 but kobs < kB at pH 8.0 and kobs increased with the fraction of stearylamine in the liposomes. However, when ASA was added via the organic phase, reactions occurred which resulted in the loss of ASA as a function of the time period between phase admixture and the point of film hydration. A product of the reactions was determined by IR and TLC to be N-stearylacetamide. Both the initial loss of ASA and the increase in stability decreased as the DMPC: stearylamine mole ratio increased. A mechanism of aminolysis occurring in the organic solvent and at liposome surfaces between ASA and stearylamine or DMPC at pH 8.0 has been suggested. It is concluded that the orientation of ASA and the ordered structural environment of the bilayers minimizes the aminolytic and hydrolytic reactions.
Habib
M J
MJ
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Rogers
J A
JA
D000588:Amines / Q000737:chemistry*; D001241:Aspirin / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002725:Chloroform / Q000737:chemistry; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008081:Liposomes; D012996:Solutions
D000588:Amines; D008081:Liposomes; D012996:Solutions; D002725:Chloroform; C009317:stearylamine; D001241:Aspirin; D004134:Dimyristoylphosphatidylcholine