Pharmaceutical composition for controlled release of treprostinil

A pharmaceutical composition, comprising:

• one or more liposome suspended in an external medium, said liposome comprising:
• (a) an external lipid bilayer, comprising at least one vesicle-forming phospholipid, wherein the vesicle-forming lipid consists of a mixture of a first phospholipid selected from the group consisting of phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylinositol (PI), phosphatidic acid (PA), phosphatidyethanolamine (PE), phosphatidylserine (PS) and any combination thereof and a second phospholipid selected from the group consisting of a PEG modified phospholipid, a positively charged or a negatively charged phospholipid, a charged lipid and any combination thereof;
• and
• (b) an internal aqueous medium, comprising treprostinil and a salt to provide a pH gradient between the internal aqueous medium and the external medium, said salt is a weak acid salt or an amino acid,
• wherein the weight ratio of treprostinil to the at least one vesicle-forming phospholipid is equal to or higher than about 0.035 and about less than 60% of the treprostinil is released within 2 hours after the administration of the pharmaceutical composition and more than 80% of the treprostinil is released more than 2 hours to about 72 hours after the administration of the pharmaceutical composition.