Liposomes with a negative excess charge

A process for the production of unilamellar liposomes containing a pharmaceutical active substance, wherein the liposomes contain 30 to 50 mol % cholesterol, 49 to 56 mol % of at least one first phospholipid and 1 to 14 mol % of at least one second phospholipid of the general formula I ##STR6## or salts thereof in relation to the total lipid components of the liposomes, in which R.sup.1 and R.sup.2 are the same or different and represent hydrogen, C.sub.1 -C.sub.4 alkyl groups or saturated or unsaturated C.sub.8 -C.sub.24 acyl groups which are unbranched or branched or/and unsubstituted or substituted, provided that at least one of the residues R.sup.1 and R.sub.2 is an acyl group as defined above, the process comprising:

• (a) dissolving the at least one second phospholipid of the general formula I, the cholesterol and the at least one first phospholipid in a solvent, wherein the at least one first phospholipid of general formula I, the cholesterol and the at least one second phospholipid amount to 100 mol %,
• (b) removing the solvent in a vacuum to produce a finely dispersed lipid film,
• (c) mixing the finely dispersed lipid film with an aqueous buffer solution to form a lipid suspension, wherein the aqueous buffer solution comprises the pharmaceutical active substance,
• (d) heating the lipid suspension, and
• (e) forming liposomes from the lipid suspension of step (d) whereby liposomes containing the pharmaceutical active substance are produced, and thereafter filtering the liposomes through a filter having a pore diameter of 0.2 .mu.m.

A process for the production of unilamellar liposomes containing a water-insoluble pharmaceutical active substance, wherein the liposomes contain 30 to 50 mol % cholesterol, 49 to 56 mol % of at least one first phospholipid and 1 to 14 mol % of at least one second phospholipid of the general formula I ##STR7## or salts thereof in relation to the total lipid components of the liposomes, in which R.sup.1 and R.sup.2 are the same or different and represent hydrogen, C.sub.1 -C.sub.4 alkyl groups or saturated or unsaturated C.sub.8 -C.sub.24 acyl groups which are unbranched or branched or/and unsubstituted or substituted, provided that at least one of the residues R.sup.1 and R.sup.2 is an acyl group as defined above, the process comprising:

• (a) dissolving the at least one of second phospholipid of the general formula I, the cholesterol, the at least one first phospholipid and the water-insoluble active substance in a solvent, wherein the at least one second phospholipid of general formula I, the cholesterol and the at least one first phospholipid amount to 100 mol %,
• (b) removing the solvent in a vacuum to produce a finely dispersed lipid film,
• (c) mixing the finely dispersed lipid film with an aqueous buffer solution to form a lipid suspension,
• (d) heating the lipid suspension, and
• (e) forming liposomes from the lipids suspension of step (d) whereby liposomes containing the water-insoluble active substance are produced, and thereafter filtering the liposomes through a filter having a pore diameter of 0.2 .mu.m.