Multiparticulate including pharmaceutical or probiotic active ingredients for delivery via a shelf stable liquid dosage form

Abstract

Various embodiments of modified-release multiparticulates (in bead or granule from) are described. The modified-release multiparticulates can comprise a core including a pharmaceutical and/or probiotic agent, optionally with additional excipients or binders to aid in creation of the core, one or more functional coatings disposed on the core and configured to provide a modified-release profile of the pharmaceutical and/or probiotic agent when given orally, and a coating of hypromellose acetate succinate (HPMCAS) disposed on the one or more functional coatings and configured to impart multiparticulate stability in aqueous acidic media. Suspensions including the modified-release multiparticulates are also described.

1 . A modified-release multiparticulate, comprising:
 a core consisting of one or more active ingredients and one or more excipients, wherein at least one of the one or more active ingredients is a probiotic;   at least one functional layer encapsulating the core; and   an exterior coating layer encapsulating the core and the at least one functional layer, the exterior coating comprising hypromellose acetate succinate.   
     
     
         2 . (canceled) 
     
     
         3 . The modified-release multiparticulate of  claim 1 , wherein the one or more excipients are non-swelling excipients. 
     
     
         4 . The modified-release multiparticulate of  claim 1 , wherein the at least one functional layer comprises an enteric polymer, an enteric resin, an insoluble cellulose-based polymer, a combination insoluble cellulose-based polymer system with a water-soluble pore former, a protein-based coating, a lipid coating, or combinations thereof. 
     
     
         5 . The modified-release multiparticulate of  claim 1 , wherein the at least one functional layer is constituted so as to not alter the release profile of the modified-release multiparticulate 
     
     
         6 . The modified-release multiparticulate of  claim 1 , wherein the exterior coating consists of hypromellose acetate succinate. 
     
     
         7 . The modified-release multiparticulate of  claim 1 , wherein the hypromellose acetate succinate comprises hydroxypropyl methylcellulose that has been further modified with a mixture of monosuccinic acid and acetic acid esters. 
     
     
         8 . The modified-release multiparticulate of  claim 1 , wherein the hypromellose acetate succinate has between 2 wt % to 16 wt % of acetyl groups and 4 wt % to 28 wt % of succinyl groups. 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . A modified-release multiparticulate, comprising:
 a core consisting one or more active ingredients, wherein at least one of the one or more active ingredients is a probiotic;   at least one functional layer encapsulating the core; and   an exterior coating layer encapsulating the core and the at least one function layer.   
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . The modified-release multiparticulate of  claim 11 , wherein the exterior coating comprises hypromellose acetate succinate, cellulose acetate phthalate (CAP), or combination thereof. 
     
     
         15 . The modified-release multiparticulate of  claim 14 , wherein the hypromellose acetate succinate comprises hydroxypropyl methylcellulose that has been further modified with a mixture of monosuccinic acid and acetic acid esters. 
     
     
         16 . The modified-release multiparticulate of  claim 14 , wherein the hypromellose acetate succinate has between 2 wt % to 16 wt % of acetyl groups and 4 wt % to 28 wt % of succinyl groups. 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . A suspension comprising:
 an acidic aqueous liquid media; and   a plurality of the modified release multiparticulate of  claim 1  suspended in the acidic aqueous liquid media.   
     
     
         20 . A suspension comprising:
 an acidic aqueous liquid media; and   a plurality of the modified release multiparticulate of  claim 11  suspended in the acidic aqueous liquid media.