Spray freeze-dried compositions

Abstract

A process for producing a powder comprises spray freeze-drying an aqueous solution or suspension comprising a pharmaceutical agent, said solution or suspension having a solids content of 20% by weight or more. The spray freeze-dried powder may be administered to a subject via a needleless syringe.

1 . A process for the preparation of a powder, which process comprises the step of spray freeze-drying an aqueous solution or suspension comprising a pharmaceutical agent, said solution or suspension having a solids content of 20% by weight or more.  
   
   
       2 . A process according to  claim 1 , wherein the solution or suspension has a solids content of 30% by weight or more.  
   
   
       3 . A process according to  claim 2 , wherein the solids content is 40% by weight or more.  
   
   
       4 . A process according to  claim 1 , wherein the pharmaceutical composition is an antigen.  
   
   
       5 . A process according to  claim 4 , wherein the antigen is adsorbed in an aluminum salt or calcium salt adjuvant.  
   
   
       6 . A process according to  claim 4 , wherein the antigen is a bacterial or viral antigen.  
   
   
       7 . A process according to  claim 1 , wherein the solution or suspension further comprises (a) an amorphous excipient selected from the group consisting of monosaccharides, disaccharides, oligosaccharides and polysaccharides; and (b) a crystalline excipient selected from the group consisting of carbohydrates, sugars and sugar alcohols.  
   
   
       8 . A process according to  claim 1 , wherein the solution or suspension further comprises (a) an amorphous excipient selected from the group consisting of dextrose, sucrose, lactose, trehalose, cellobiose, raffinose, isomaltose and cyclodextrins, and (b) mannitol as a crystalline excipient.  
   
   
       9 . A process according to  claim 7 , wherein the solution or suspension further comprises (c) a polymer.  
   
   
       10 . A process according to  claim 9 , wherein the polymer is dextran.  
   
   
       11 . A process according to  claim 7 , wherein the solution or suspension further comprises (d) an amino acid or a physiologically acceptable salt thereof.  
   
   
       12 . A process according to  claim 7 , wherein the solution or suspension further comprises (c) a polymer and (d) an amino acid or physiologically acceptable salt thereof.  
   
   
       13 . A process according to  claim 1 , wherein the solution or suspension further comprises trehalose, mannitol and dextran in a weight ratio of from about 3:3:4 to about 4:4:3.  
   
   
       14 . A process according to  claim 1 , wherein the solution or suspension is sprayed from an ultrasonic nozzle.  
   
   
       15 . A process according to  claim 1 , wherein the solution or suspension is sprayed into liquid nitrogen.  
   
   
       16 . A process according to  claim 1 , wherein the solution or suspension is sprayed into a liquified gas and the liquified gas containing the resulting frozen droplets of the solution or suspension is subjected to a two stage drying process comprising: 
 (i) a first drying stage which is performed at a temperature of from about −50° C. to 0° C. for a period of about 4 to 24 hours under a pressure of about 20 to 500 mT; and    (ii) a second drying stage which is performed at a temperature of from about 5 to 30° C. for a period of about 5 to 24 hours under a pressure of less than 100 mT.    
   
   
       17 . A process according to  claim 1 , wherein the resulting spray freeze-dried particles are collected, washed and dried.  
   
   
       18 . A process according to  claim 17 , wherein the dried particles are sieved.