SOLUBILIZATION OF MULTILAMELLAR LIPOSOMES IN THE PRESENCE OF NON-IONIZED DRUG

The solubilization of multilamellar liposomes by metoprolol tartrate ( MPL) has been studied as a function of pH, [MPL], [dimyristoylphosphat idylcholine (DMPC)], temperature and lipid composition. The solubiliza tion of liposomes at 37-degrees-C by 7.3 mm MPL occurred at different rates at different pH values. MPL completely solubilized by 72 mM DMPC liposomes after about 17 h at pH 12, but only a partial solubilizatio n occurred at pH 10 and 11. Between pH 7 and 9 no change in turbidity was observed after 1 week. Addition of cholesterol (CHOL) to DMPC (2:1 mol) had very little effect on solubilization after 24 h, however wit h DMPC:CHOL (5:1 mol) the decrease in turbidity was observed after 24 h, even though solubilization was much less compared with that of DMPC alone. The rate of solubilizaiton was decreased when dipalmitoylphosp hatidylcholine liposomes were employed. Addition of dicetylphosphate ( DCP) to DMPC liposomes reduced the rate of solubilization significantl y. The solubilization of liposomes by 7.3 mm MPL as a function of [DMP C], indicated that the lower the liposome concentration the greater th e effect on solubilization. It is concluded that MPL in the non-ionize d form has a solubilizing effect on liposomes, and addition of CHOL or DCP to DMPC has a stabilizing effect against solubilization.