Multiparticulate granulate comprising insulin

Abstract

The present invention is directed to multiparticulate granulate compositions comprising particles of insulin and particles of an infant nutritional excipient, wherein the multiparticulate granulate is substantially free of layers of insulin and excipient, methods of making thereof, and methods of use thereof.

1 . A composition-of-matter comprising particles of insulin dispersed on particles of an infant nutritional excipient. 
     
     
         2 . (canceled) 
     
     
         3 . The composition-of-matter of  claim 1 , wherein the infant nutritional excipient comprises maltodextrin. 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . The composition-of-matter of  claim 1 , having a particle size ranging from about 125 μm to about 1000 μm and an average particle size ranging from about 200 μm to about 600 μm, monomodal distribution. cm  7 - 11 . (canceled) 
     
     
         12 . The composition-of-matter of  claim 1 , wherein a ratio of the particles of infant nutritional excipient to the particles of insulin ranges from about 2,500:1 to about 750,000:1. 
     
     
         13 . The composition-of-matter of  claim 1 , wherein the amount of insulin in the particles of insulin ranges from about 0.0001 wt. % to about 0.04 wt. %. 
     
     
         14 . The composition-of-matter of  claim 1 , having a moisture content of is no more than about 6.5 wt. %. 
     
     
         15 . The composition-of-matter of  claim 1 , wherein the particles of insulin include no more than about 5 wt. % A-21 desamido human insulin. 
     
     
         16 . The composition-of-matter of  claim 1 , wherein the particles of insulin include no more than about 15 wt. % total related proteins. 
     
     
         17 . (canceled) 
     
     
         18 . The composition-of-matter of  claim 1 , having a bulk uniformity of about 90-20% with an RSD of not more than about 5%. 
     
     
         19 . The composition-of-matter of  claim 1 , wherein at least 80% of the composition-of-matter dissolves within 5 minutes when dispersed in 2/3 by wt. 0.9% saline at 25° C. 
     
     
         20 . The composition-of-matter of  claim 1 , wherein the insulin concentration is 0.04-8. 
     
     
         21 - 27 . (canceled) 
     
     
         28 . The composition-of-matter of  claim 1 , having a flow index of 10-30 seconds per 1.00 g when passed through a 10 mm orifice. 
     
     
         29 - 49 . (canceled)