Phospholipid depot

Abstract

The present invention is directed to compositions and methods of preparation of phospholipid depots that are injectable through a fine needle.

What is claimed is: 
     
         1 . A nanoemulsion based injectable one-phase gel composition, comprising:
 about 20% to about 60% by weight of a phospholipid based on the total weight of the gel, wherein the phospholipid is a member selected from the group consisting of a lecithin, phosphatidylcholine or a mixture thereof;   0.1% to 65% by weight water based on the total weight of the gel;   1% to 50% by weight of an oil based on the total weight of the gel, wherein the phospholipid comprising particles are stacked together and have a size of less than 200 nm in diameter;   wherein the composition has an increased degree of order as shown by an increase in the Scherrer crystalline domain size over a composition containing the same quantities of the same components but prepared by a process without forming a nanodispersion and the discrete phospholipid particles; and is extrudable or injectable through a 25 G, ½ inch long needle from a 1 cc syringe at an extrusion rate of 2 cc/min by an applied force of no more than 12 pounds.   
     
     
         2 . The gel composition of  claim 1 , further comprising a pharmacologically active agent having concentration of no more than 20% by weight of the final gel composition. 
     
     
         3 . The gel composition of  claim 2 , wherein the pharmacologically active agent is a heat-sensitive pharmacologically active agent. 
     
     
         4 . The gel composition of  claim 2 , wherein the pharmacologically active agent is a protein or peptide. 
     
     
         5 . The gel composition of  claim 2 , wherein the pharmacologically active agent is a member selected from the group consisting of an insulin, an insulin analog, a crystalline insulin with zinc and/or protamine, an NPH insulin, and a combination thereof. 
     
     
         6 . The gel composition of  claim 1 , wherein the phospholipid comprises 20% to 40% by weight based on the total weight of the gel. 
     
     
         7 . The gel composition of  claim 1 , wherein the phospholipid is a lecithin. 
     
     
         8 . The gel composition of  claim 1 , wherein the oil is selected from the group consisting of a synthetic oil, a vegetable oil, a medium chain oil, ethyl oleate, fatty acid, vitamin E, vitamin E succinate, cholesterol, or a mixture thereof. 
     
     
         9 . The gel composition of  claim 1 , further comprising one or more sugars selected from the group consisting of sucrose, dextrose, lactose, glucose, trehalose, maltose, mannitol, sorbitol, glycerol, amylose, starch, amylopectin, or a mixture thereof. 
     
     
         10 . The gel composition of  claim 1 , further comprising one or more non-aqueous solvents selected from the group consisting of ethanol, propylene glycol, glycerol, sorbitol, polyethylene glycol, ethyl oleate, or a mixture thereof. 
     
     
         11 . The gel composition of  claim 1 , further comprising a functional pharmaceutical excipient selected from the group consisting of an acidifying agent, an alkalizing agent, a pH buffering agent, a metal ion chelator, an antioxidant, a preservative, a tonicity/osmotic pressure modifier, a condensing agent, a solubilizing agent, or a mixture thereof. 
     
     
         12 . The gel composition of  claim 1 , wherein the gel composition has a small-angle X-ray scattering diffractogram of  FIG. 10  and a lattice d spacing of 67 Å and 33 Å.