Formulation of Fine Particles Using Liquefied or Dense Gases

Abstract

The invention provides a method for manipulating or formulating a solid substance which melts under pressure of a gas without degrading at a temperature lower than the melting point of the substance at atmospheric pressure including: applying to the substance a liquefied gas or dense gas to melt the substance without degrading the substance; then contacting the molten substance with a carrier fluid, which is at substantially the same pressure as the liquefied gas or dense gas, to form a solution or mixture of at least a part of the molten substance and the carrier fluid; and passing the solution or mixture into a vessel of lower pressure than the pressure of the liquefied gas or dense gas and carrier fluid to form particles of the substance; and particles formed by the method.

1 . A method for manipulating or formulating a solid substance which melts under pressure of a gas without degrading at a temperature which is lower than the melting point of the substance at atmospheric pressure including:
 applying to the substance a liquefied gas or dense gas to melt the substance without degrading the substance;   then contacting the molten substance with a carrier fluid, which is at substantially the same pressure as the liquefied gas or dense gas, to form a solution or mixture of at least a part of the molten substance and the carrier fluid; and   passing the solution or mixture into a vessel of lower pressure than the pressure of the liquefied gas or dense gas and carrier fluid to form particles of the substance.   
     
     
         2 . A method according to  claim 1 , wherein over 50% of the particles are less than 5000 nanometers in diameter. 
     
     
         3 . Particles of a substance formed by a method according to  claim 1 . 
     
     
         4 . Encapsulated particles of a substance formed by a method according to  claim 2 . 
     
     
         5 . Particles according to  claim 3 , wherein the particles include a pharmaceutical or biological substance. 
     
     
         6 . Particles according to  claim 5 , wherein the particles include primarily cyclosporine. 
     
     
         7 . Particles according to  claim 3 , wherein at least 50% of the particles are between 50 and 5000 nanometers in diameter. 
     
     
         8 . A composition suitable for aerosol delivery including particles formed by a method according to  claim 1 . 
     
     
         9 . A method according to  claim 7 , wherein the administration is by transdermal application, oral, controlled or sustained release. 
     
     
         10 . A pharmaceutical composition including particles of a substance produced by a method according to  claim 1 . 
     
     
         11 . A pharmaceutical composition according to  claim 10 , wherein the substance is a pharmaceutical or biological compound. 
     
     
         12 . A pharmaceutical composition according to  claim 10 , wherein the substance is cyclosporine. 
     
     
         13 . Particles according to  claim 3 , wherein the particles include primarily gemfibrozil or fenofibrate. 
     
     
         14 . A pharmaceutical composition according to  claim 10 , wherein the substance is gemfibrozil or fenofibrate.