Pharmaceutical compositions comprising ferric citrate and methods for the production thereof

Abstract

The present invention relates to a pharmaceutical composition comprising granules which include an inert core coated with ferric citrate. The present invention also provides methods of manufacture thereof and methods of use thereof.

1 - 45 . (canceled) 
     
     
         46 . A solid pharmaceutical composition comprising:
 a. granules comprising an inert core and a layer over said core, said layer comprising ferric citrate in an amount of at least about 50 wt % based on the weight of said composition, and optionally a binder; and   b. optionally, at least one pharmaceutically acceptable excipient;   
       wherein the composition is characterized by an in vitro dissolution rate in which at least 85% of the ferric citrate drug is released within about 15 minutes. 
     
     
         47 . The composition of  claim 46 , wherein the granules are milled. 
     
     
         48 . The composition of  claim 46 , wherein the inert core comprises microcrystalline cellulose. 
     
     
         49 . The composition of  claim 46 , which comprises a binder in the ferric citrate layer. 
     
     
         50 . The composition of  claim 49 , wherein the binder is selected from the group consisting of povidone (PVP), hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), sodium alginate, alginic acid, guar gum, acacia gum, xanthan gum, carbopol, carboxymethyl cellulose, ethyl cellulose, maltodextrin, vinylpyrrolidone/vinyl acetate copolymer, microcrystalline cellulose, starch, and methyl cellulose, or any combination thereof. 
     
     
         51 . The composition of  claim 46 , which comprises a pharmaceutically acceptable excipient which is an intra-granular excipient, an extra-granular excipient, or a combination thereof. 
     
     
         52 . The composition of  claim 51 , wherein the pharmaceutically acceptable excipient is selected from the group consisting of a binder, a disintegrating agent, a filler, an anti-tacking agent, a lubricant, a glidant, a surfactant, a plasticizer and any combination thereof. 
     
     
         53 . The composition of  claim 52 , wherein the filler is selected from the group consisting of a sugar, microcrystalline cellulose, dicalcium phosphate, a sugar alcohol, a hydrogenated starch hydrolysate, a starch, sodium carboxymethycellulose, ethyl cellulose, and cellulose acetate, or any combination thereof. 
     
     
         54 . The composition of  claim 52 , wherein the disintegrating agent is selected from the group consisting of low-substituted carboxymethyl cellulose sodium, cross-linked polyvinyl pyrrolidone (crospovidone), sodium starch glycolate, cross-linked sodium carboxymethyl cellulose, pregelatinized starch, microcrystalline starch, water insoluble starch, calcium carboxymethyl cellulose, low substituted hydroxypropyl cellulose, and magnesium aluminum silicate, or any combination thereof. 
     
     
         55 . The composition of  claim 52 , wherein the glidant is selected from the group consisting of corn starch, a silica derivative, silicon dioxide, anhydrous silica, and talc, or any combination thereof. 
     
     
         56 . The composition of  claim 52 , wherein the lubricant is selected from the group consisting of magnesium stearate, calcium stearate, oleic acid, caprylic acid, stearic acid, magnesium isovalerate, calcium laurate, magnesium palmitate, behenic acid, glyceryl behenate, glyceryl stearate, sodium stearyl fumarate, potassium stearyl fumarate, zinc stearate, sodium oleate, sodium stearate, sodium benzoate, sodium acetate, sodium chloride, talc, solid polyethylene glycol, and hydrogenated vegetable oil, or any combination thereof. 
     
     
         57 . The composition of  claim 52 , wherein the binder is an extra-granular excipient. 
     
     
         58 . The composition of  claim 46 , in a form suitable for oral administration selected from the group consisting of a tablet, a capsule, a pill, a powder, and a pellet. 
     
     
         59 . The composition of  claim 58 , in the form of a tablet. 
     
     
         60 . The composition of  claim 59 , further comprising at least one coating layer. 
     
     
         61 . The composition of  claim 60 , wherein the coating layer is an immediate release coating. 
     
     
         62 . The composition of  claim 59 , wherein the tablet is characterized by having friability of less than about 1%. 
     
     
         63 . The composition of  claim 46 , comprising from about 500 mg to about 1,500 mg ferric citrate. 
     
     
         64 . The composition of  claim 46 , which is characterized by an in vitro dissolution rate in which at least 85% of the ferric citrate drug is released within about 15 minutes after storage of the composition at accelerated storage conditions at 40° C. and 75% relative humidity for three months. 
     
     
         65 . A method for treating a disorder or a medical condition selected from the group consisting of renal insufficiency, renal failure, hyperphosphatemia, metabolic acidosis, calcium phosphate deposition, calcification of soft tissue, kidney stones, elevated serum calcium levels and anemia, the method comprising the step of administering to a subject in need thereof a pharmaceutical composition according to  claim 46 .