Formulations of creatine and cyclodextrin exhibiting improved bioavailability

Abstract

Formulations of creatine, preferably phosphocreatine and most preferably disodium phosphocreatine, combined with cyclodextrin exhibit improved uptake across digestive mucosa, including intestinal, esophageal, and stomach mucosa. In particular, the formulations of the present invention are designed for protection of the creatine as they come in contact with gastric juices so as to allow thereafter for unexpectedly improved site-specific intestinal release.

1 . A method of manufacturing a creatine supplement comprising:
 co-granulating one or more creatine compounds, cyclodextrin, and a sodium source to form a granular composition having an average particle size of from 150 to 850 microns; and   coating the granular composition with methacrylate copolymers to produce a coated creatine supplement.   
     
     
         2 . The method of  claim 1 , wherein the one or more creatine compounds comprises phosphocreatine and the sodium source comprises trisodium citrate. 
     
     
         3 . The method of  claim 1 , wherein the one or more creatine compounds comprises disodium phosphocreatine and the disodium moiety of the phosphocreatine constitutes all or part of the sodium source. 
     
     
         4 . The method of  claim 1 , wherein the creatine compound is selected from the group consisting of creatine monohydrate, creatine HCl and phosphocreatine, and sodium of the sodium source is present in a molar ratio of sodium to creatine of from 1:1 to 3:1. 
     
     
         5 . The method of  claim 1 , wherein the creatine supplement comprises disodium phosphocreatine and cyclodextrin selected from the group consisting of alpha, beta and gamma cyclodextrins. 
     
     
         6 . The method of  claim 1 , wherein the creatine supplement comprises:
 (i) at least one of disodium phosphocreatine or phosphocreatine;   (ii) polyethylene glycol; and   (iii) cyclodextrin selected from the group consisting of alpha, beta and gamma cyclodextrins.   
     
     
         7 . The method of  claim 1 , wherein the creatine supplement is coated with Eudraguard® as the methacrylate copolymer coating. 
     
     
         8 . The method of  claim 1 , wherein the creatine supplement comprises 85% disodium phosphocreatine, 5% polyethylene glycol, 5% cyclodextrins and is coated with a 5% by weight of the formulation coating comprising methacrylate copolymer. 
     
     
         9 . The method of  claim 1 , wherein the coating step comprises spray drying the granular compound utilizing a fluidized bed technique. 
     
     
         10 . The method of  claim 1 , wherein the creatine supplement is used for treating a muscle wasting disorder. 
     
     
         11 . The method of  claim 1 , wherein the creatine supplement is used to enhance body muscle mass for sports performance applications, sports injury recovery or for maintenance of normal muscle tone during the aging process of a mammal. 
     
     
         12 . A method of manufacturing a creatine supplement comprising:
 co-granulating a plurality of the following:
 (i) one or more creatine compounds; 
 (ii) cyclodextrin; or 
 (iii) a sodium source; 
   forming a granular composition having an average particle size of from 150 to 850 microns; and   coating the granular composition with methacrylate copolymers to produce a coated creatine supplement.   
     
     
         13 . The method of  claim 12 , further comprising:
 the one or more creatine compounds comprises disodium phosphocreatine;   the cyclodextrin is selected from the group consisting of alpha, beta and gamma cyclodextrins; and   the sodium source comprises trisodium citrate.   
     
     
         14 . The method of  claim 12 , wherein the sodium source comprises trisodium citrate present in a molar ratio of sodium to creatine from the creatine compound of from 1:1 to 3:1. 
     
     
         15 . The method of  claim 12 , wherein the cyclodextrin is present in a range of from 1% to 10% (w/w). 
     
     
         16 . The method of  claim 12 , wherein the creatine supplement is coated with Eudraguard® as the methacrylate copolymer coating. 
     
     
         17 . A method of manufacturing a creatine supplement comprising:
 co-granulating a plurality of the following:
 (i) creatine monohydrate, creatine HCL and/or phosphocreatine; 
 (ii) cyclodextrins selected from the group consisting of alpha, beta and gamma cyclodextrins; or 
 (iii) a sodium source; 
   forming a granular composition having an average particle size of from 150 to 850 microns; and   coating the granular composition with methacrylate copolymers to produce a coated creatine supplement.   
     
     
         18 . The method of  claim 17 , further comprising:
 the phosphocreatine being disodium phosphocreatine;   the cyclodextrins being a mixture selected from the group consisting of alpha, beta and gamma cyclodextrins;   the sodium source comprising trisodium citrate;   the methacrylate copolymers being Eudraguard®; and   the addition of at least one of starch, maltodextrin, and polyethylene glycol to the co-granulation prior to coating.   
     
     
         19 . The method of  claim 18 , further comprising:
 the disodium phosphocreatine present from 75% to 95% (w/w);   the mixture of cyclodextrins present from 1% to 10% (w/w);   the trisodium citrate present in a molar ratio of sodium to creatine from the creatine compound of from 1:1 to 3:1;   the Eudraguard® present from 1% to 10% (w/w/); and   the polyethylene glycol being PEG 3350 present from 1% to 10% (w/w).   
     
     
         20 . The method of  claim 18 , further comprising:
 the disodium phosphocreatine present from 75% to 95% (w/w);   the mixture of cyclodextrins present from 0.1% to 10% (w/w);   the trisodium citrate present in a molar ratio of sodium to creatine from the creatine compound of from 1:20 to 20:1;   the Eudraguard® present from 1% to 10% (w/w); and   the polyethylene glycol being PEG 3350 present from 0.1% to 10% (w/w).