Synthesis of Small Particles

Abstract

The invention provides an apparatus for forming fine particles of a substance in a precipitation chamber, in which the apparatus has means to convey the fine particles from the precipitation chamber to at least one particle collection chamber, downstream of the precipitation chamber, the particle collection chamber having an inlet and an outlet separate from the inlet. The invention also provides a method of forming fine particles of a substance, the method comprising contacting a non-gaseous fluid containing the substance with a dense fluid to expand the non-gaseous fluid in a precipitation chamber, conveying a resulting mixture of fluid and the fine particles from the precipitation chamber to a collection chamber, the collection chamber having an inlet and an outlet separate from the inlet.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising fine particles of a biologically active substance produced by contacting a non-gaseous fluid containing the substance with a dense fluid to expand the non-gaseous fluid in a precipitation chamber to form the fine particles, conveying a resulting mixture of fluid and the fine particles from the precipitation chamber to a particle collection chamber by a carrying fluid, the particle collection chamber having an inlet and an outlet separate from the inlet, wherein the carrying fluid, which comprises the dense fluid and the non-gaseous fluid exerts a first force on the fine particles to convey the particles into the particle collection chamber, the collection chamber being adapted such that a second balancing force is exerted generally towards the inlet on the fine particles adjacent the outlet, wherein the particles have a particle size of between about 50 nm to 500 nm. 
     
     
         2 . The pharmaceutical composition of  claim 1  in a form for inhalation delivery, wherein the form is selected from the group consisting of a metered dose inhaler and a nebulizer. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the biologically active substance is pH sensitive. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the biologically active substance is insulin. 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein at least 42% of the fine particles produced have a particle size of between about 50 nm to 500 nm. 
     
     
         6 . A method of treatment of a subject, the method comprising administering to the subject, an effective amount of fine particles of a biologically active substance produced by the method of  claim 1 . 
     
     
         7 . The method of  claim 6 , wherein the biologically active substance is insulin. 
     
     
         8 . A pharmaceutical composition comprising fine particles of a biologically active substance produced by contacting a non-gaseous fluid containing the substance with a dense fluid to expand the non-gaseous fluid in a precipitation chamber to form the fine particles, conveying a resulting mixture of fluid and the fine particles from the precipitation chamber to a particle collection chamber by a carrying fluid, the particle collection chamber having an inlet and an outlet separate from the inlet, wherein the carrying fluid, which comprises the dense fluid and the non-gaseous fluid exerts a first force on the fine particle to convey the particles into the particle collection chamber, the collection chamber being adapted such that a second balancing force is exerted generally towards the inlet on the fine particles adjacent the outlet, wherein the biologically active substance is pH sensitive and selected from the group consisting of a polypeptide, peptide, peptide analog and peptidomimetic. 
     
     
         9 . The pharmaceutical composition of  claim 8  in a form for inhalation delivery, wherein the form is selected from the group consisting of a metered dose inhaler and a nebulizer. 
     
     
         10 . The pharmaceutical composition of  claim 8 , wherein the particles have a particle size of about 1-5 μm. 
     
     
         11 . A method of treatment of a subject, the method comprising administering to the subject, an effective amount of fine particles of the biologically active substance of  claim 8 .