Methods and apparatus for making liposomes containing hydrophobic drugs

DETAILED DESCRIPTION The present invention features methods and apparatus for producing liposomes containing hydrophobic drugs.
Examples of hydrophobic drugs comprise taxoids, camptothecins, doxorubicin, michellamine B, vincristine, bryostatin-1, halomon, and cisplatin.
The methods and apparatus are suitable for large scale production of pharmaceutical grade liposomes which are sterile, of a predetermined size, and are substantially free of organic solvents.
The present invention features several different methods of making liposomes using critical, supercritical or near critical fluids.
One method comprises the steps of forming a solution or mixture of a phospholipid, a hydrophobic drug, an aqueous phase and a critical, supercritical or near critical fluid.
The solution or mixture is decompressed to separate the critical, supercritical or near critical fluid, from the phospholipid and aqueous medium, to form one or more liposomes.
This method is referred to as the decompression method of forming liposomes in several examples.
Preferably, the rate of depressurization influences the size of the liposomes formed.
As used herein, the term "phospholipid" refers to compositions which are esters of fatty acids in which the alcohol component of the molecule contains a phosphate group as an integral part.
Phospholipids comprise the glycerophosphatides, containing glycerol, and the sphingomyelins containing sphingosine.
Preferred phospholipids comprise phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and sphingomyelin; and synthetic phospholipids comprising dimyristoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearoyl phosphatidylcholine, distearoyl phosphatidylglycerol, dipalmitoyl phosphatidylglycerol, dimyristoyl phosphatidylserine, distearoyl phosphatidylserine, and dipalmitoyl serine.
In the field of physical chemistry, the term "critical fluid" refers to a substance at or above its critical temperature and at or above its critical pressure.
The term "supercritical fluid" refers to a substance above its critical temperature and above its critical pressure