Multiparticulate formulations of lithium salts for oral administration suitable for once-a-day administration

Abstract

This invention refers to: multiparticulate formulations of Lithium salts for oral administration constituted by either modified release granules or mixtures of modified and conventional release granules, suitable for once-a-day administration also at high strengths of Lithium salts, and to the preparation process of said formulations.

1 ) A multiparticulate formulation comprising a plurality of microgranules or micro-tablets having dimensions ranging from 200 to 2000 micrometers and each microgranule or microtablet containing granulated Lithium salts and a binder, said plurality of microgranules or micro-tablets being coated microgranules or microtablets having a modified release, said formulation having a Lithium salt content of at least 500 mg/g and said mixture having sufficient modified release coated microgranules or microtablets to have an in vitro dissolution profile suitable for once-a-day administration.  
   
   
       2 ) The formulation according to  claim 1 , wherein the Lithium salt content is up to 1000 mg per dose.  
   
   
       3 ) The formulation according to  claim 1 , wherein said Lithium salt content is at least 900 mg/g.  
   
   
       4 ) The formulation according to  claim 1 , wherein said Lithium salt is selected from the group consisting of lithium carbonate, acetate, glutamate, thionate and sulphate.  
   
   
       5 ) The formulation according to  claim 1 , wherein the modified release microgranules or microtablets are coated with a substance selected from the group consisting of polymers of acrylic and methacrylic acid, cellulose derivatives, stearic acid, paraffin, shellac, zein, or mixtures of the same in any proportion, optionally charged with therapeutically acceptable plasticizers.  
   
   
       6 ) The formulation according to  claim 5 , wherein said polymers of acrylic and methacrylic acid are selected from the group consisting of poly (methacrylic acid-co-ethyl acrylate), 1:1, 250,000 MW, poly (ethyl acrylate-co-methyl methacrylate-co-trimethyl ammonioethyl methacrylate chloride), 1:2:0.1, 150,000 MW, and poly (ethyl acrylate-co-methyl methacrylate-co-trimethyl ammonioethyl methacrylate chloride), 1:2:0.2, 150,000 MW.  
   
   
       7 ) The formulation according to  claim 5 , wherein said cellulose derivatives are selected from the group consisting of ethylcellulose, hydroxypropylmethylcellulose, hydroxypropylmethylcellulosephtalate, celluloseacetatephtalate.  
   
   
       8 ) The formulation according to  claim 1  wherein the binder is polyvinylpyrolidone.  
   
   
       9 ) The formulation according to  claim 1  further comprising talc.  
   
   
       10 ) A multiparticulate formulation comprising a plurality of microgranules or micro-tablets having dimensions ranging from 200 to 2000 micrometers and each microgranule or microtablet containing granulated Lithium salts and a binder, said plurality of microgranules or micro-tablets being coated microgranules or microtablets having a modified release, said formulation having a Lithium salt content of at least 500 mg/g and said mixture having sufficient modified release coated microgranules or microtablets to have an in vitro dissolution profile suitable for once-a-day administration, said binder being polyvinlypyrolidone, said coating being ethylcellulose, said lithium salt being lithium carbonate, said formulation containing talc.  
   
   
       11 ) The formulation of  claim 10  wherein the formulation has a mixture of ingredients in a ratio comparable to a formulation composed of about 8 kg of lithium carbonate, 2.4 kg polyvinylpyrollidone, 11.7 kg ethylcellulose, and 84.5 g talc.  
   
   
       12 ) The formulation of  claim 10  wherein the formulation contains 95.47% wt lithium carbonate, 1.79% polyvinylpyrollidone, 0.49% magnesium stearate, 1.47% ethylcellulose, 0.29% diethyl phthalate, and 0.49% talc.  
   
   
       13 ) The formulation according to  claim 1  wherein the formulation has an amount of modified release microgranules or microtablets sufficient to have a dissolution profile where from 5-25% of the Lithium salt is dissolved in one hour, 20-45% is dissolved in four hours, 40-65% is dissolved in eight hours, 50-80% is dissolved in twelve hours; and 60-90% is dissolved in twenty four hours.  
   
   
       14 ) The formulation according to  claim 12  wherein the formulation has an amount of modified release microgranules or microtablets sufficient to have a dissolution profile where 7% of the lithium carbonate is dissolved in one hour, 21% is dissolved in four hours, 47% is dissolved in eight hours, 60% is dissolved in twelve hours; and 91% is dissolved in twenty four hours.