Phospholipid depot

Abstract

The present invention provides a clear depot comprising at least one hydrophilic water-soluble pharmaceutically active agent selected from the group consisting of vancomycin, gentamicin, a pharmaceutically acceptable salt thereof and a mixture thereof, water, a phospholipid, an oil, optionally a pH adjusting agent, and a viscosity modifying agent selected from the group consisting of ethanol, isopropanol, and a mixture thereof, wherein the water present in the depot is no more than about 4 wt % relative to the total weight of the depot and the depot has a pH of between about 3 and about 6, method of making and administering same.

What is claimed is: 
     
         1 . A depot composition comprising: at least one hydrophilic water-soluble pharmaceutically active agent selected from the group consisting of vancomycin, gentamicin, and pharmaceutically acceptable salts thereof; water; a phospholipid; an oil; and a viscosity modifying agent; wherein said composition is characterized by a major endothermic event up to about 100° C. 
     
     
         2 . The depot of  claim 1 , wherein said phospholipid is present in the depot from about 5 wt % to about 95 wt %. 
     
     
         3 . The depot of  claim 1 , wherein said phospholipid is present in the depot from about 25 wt % to about 75 wt %. 
     
     
         4 . The depot of  claim 1 , wherein said phospholipid is present in the depot from about 35 wt % to about 60 wt %. 
     
     
         5 . The depot of  claim 1 , wherein said oil is selected from the group consisting of: vegetable oil, animal oil, and a mixture thereof. 
     
     
         6 . The depot of  claim 1 , wherein said oil present in the depot is from about 5 wt % to about 95 wt %. 
     
     
         7 . The depot of  claim 1 , wherein said oil present in the depot is from about 25 wt % to about 75 wt %. 
     
     
         8 . The depot of  claim 1 , wherein said oil present in the depot is from about 35 wt % to about 60 wt %. 
     
     
         9 . The depot of  claim 1 , wherein said viscosity modifying agent is selected from the group consisting of: ethanol, isopropanol and a mixture thereof. 
     
     
         10 . The depot of  claim 1 , wherein the amount of the viscosity modifying agent in the depot is from about 1 wt % to about 20 wt % relative to the total weight of the depot. 
     
     
         11 . The depot of  claim 1 , wherein the amount of the viscosity modifying agent in the depot is from about 2 wt % to about 18 wt % relative to the total weight of the depot. 
     
     
         12 . The depot of  claim 1 , wherein said pharmaceutically acceptable salt of vancomycin and/or gentamicin is selected from the group consisting of acetate, hydrochloride, hydrobromide, citrate, formate, lactate, succinate, and sulfate. 
     
     
         13 . The depot of  claim 1 , wherein the viscosity of the depot is from about 100 centipoise to about 5000 centipoise. 
     
     
         14 . The depot of  claim 1 , wherein the pH of the depot is from about 3 to about 6. 
     
     
         15 . The depot of  claim 1 , wherein the amount of the water present in the depot is no more than about 4 wt % relative to the total weight of the depot. 
     
     
         16 . The depot of  claim 1 , wherein the amount of the water present in the depot is no more than about 2 wt % relative to the total weight of the depot. 
     
     
         17 . The depot of  claim 1 , wherein said endothermic event is elucidated by Differentiating Scanning calorimetry (DSC). 
     
     
         18 . A depot composition comprising: at least one hydrophilic water-soluble pharmaceutically active agent selected from group consisting of vancomycin, gentamicin, and pharmaceutically acceptable salts thereof; water; a phospholipid; an oil; and a viscosity modifying agent; wherein said composition releases no more than about 80% of vancomycin and/or gentamicin at two hours when measured in accordance with a USP method I using 500 ml of deionized water as a medium. 
     
     
         19 . The depot of  claim 18 , wherein said composition releases no more than about 50% of vancomycin and/or gentamicin at two hours. 
     
     
         20 . The depot of  claim 18 , wherein said composition releases no more than about 20% of vancomycin and/or gentamicin at two hours. 
     
     
         21 . A composition comprising: at least one hydrophilic water-soluble pharmaceutically active agent selected from the group consisting of vancomycin, gentamicin, and pharmaceutically acceptable salts thereof; water; a phospholipid; an oil; and a viscosity modifying agent; wherein said composition is selected from an emulsion, a primary emulsion, a nanoemulsion, a solution, dry paste, a gel, or a combination thereof. 
     
     
         22 . The composition of  claim 21 , wherein said composition is an emulsion and is prepared by a process comprising: emulsification. 
     
     
         23 . The composition of  claim 21 , wherein said composition is a primary emulsion and is prepared by homogenization of an emulsion. 
     
     
         24 . The composition of  claim 21 , wherein said solution is monophasic solution and is prepared by a process comprising preparing an emulsion, performing homogenization to obtain a primary emulsion, and performing microfludization to obtain a monophasic solution. 
     
     
         25 . The composition of  claim 21 , wherein said composition is a dry paste and is prepared by a process comprising: emulsification, homogenization of the emulsion, and microfluidization and lyophilisation to obtain a dry paste. 
     
     
         26 . The composition of  claim 21 , wherein said gel is prepared by a process comprising steps of (1) emulsification, (2) homogenization/microfluidization, (3) lyophilization, (4) dilution, (5) pre-filtration, (6) viscosity modifying agent removal and (7) filtration. 
     
     
         27 . A composition comprising: vancomycin or pharmaceutically acceptable salts thereof; water; a phospholipid; an oil; and a viscosity modifying agent; wherein said composition is an oil-in-water emulsion having an initial drug concentration of vancomycin in water from about 1 mg/ml to about 50 mg/ml. 
     
     
         28 . The composition of  claim 27 , wherein said vancomycin is vancomycin hydrochloride. 
     
     
         29 . The composition of  claim 27 , wherein said composition has an initial drug concentration of vancomycin hydrochloride in water from about 20 mg/ml to about 30 mg/ml. 
     
     
         30 . A composition comprising: gentamicin or pharmaceutically acceptable salts thereof; water; a phospholipid; an oil; and a viscosity modifying agent; wherein said composition is oil-in-water emulsion having an initial drug concentration of gentamicin in water from about 1 mg/ml to about 75 mg/ml. 
     
     
         31 . The composition of  claim 30 , wherein said gentamicin is gentamicin sulfate. 
     
     
         32 . The composition of  claim 30 , wherein said composition has an initial drug concentration of gentamicin sulfate in water from about 10 mg/ml to about 30 mg/ml. 
     
     
         33 . A method of administering a depot comprising: administering intradermally, intramuscularly, intraincisionally, subcutaneously, by instillation or topically to a wound at least one hydrophilic water-soluble pharmaceutically active agent selected from group consisting of vancomycin, gentamicin, and pharmaceutically acceptable salts thereof; water; a phospholipid; an oil; and a viscosity modifying agent. 
     
     
         34 . The method of  claim 33 , wherein said method comprises administering a depot which provides local tissue concentrations sufficient to treat and/or prevent infections at the wound. 
     
     
         35 . The method of  claim 33 , wherein said depot is sufficient to release the pharmaceutically active agent for a period of about at least one day with a dosing volume from about 0.1 mL to about 100 mL.