Solid oral dosage forms of eslicarbazepine

Abstract

The present invention relates to high drug load pharmaceutical compositions comprising eslicarbazepine or its pharmaceutically acceptable salts, esters, solvates, polymorphs, enantiomers or mixtures thereof. The present invention also relates to a process for preparing high drug load solid oral pharmaceutical composition comprising eslicarbazepine acetate and at least one pharmaceutically acceptable excipient. The prior art highlights various technical challenges for formulation development of eslicarbazepine acetate at lab as well as at industrial scale and offer restrictive and complex approach for resolution of technical challenges. Compositions of eslicarbazepine acetate prepared as per present invention, wherein disintegrant and/or binder is present in either intra-granular part or in extra-granular part of the composition exhibited desirable technical attributes like comparable dissolution and bioequivalence against reference listed drug.

We claim: 
     
         1 . A high drug load immediate release solid oral pharmaceutical composition in the form of a tablet having an intragranular portion and an extragranular portion, wherein:
 the intragranular portion comprising eslicarbazepine acetate in an amount of 80% to 95% w/w of the composition;   a binder being present in an amount of less than 3% w/w of the composition; and   a disintegrant in an amount of less than 12% w/w of the composition; and   the extragranular portion comprising a lubricant in an amount of between 0.5% and 5% w/w of the composition,   wherein the disintegrant and the binder are present in the intragranular portion of the composition and the extragranular portion of the composition is free of a disintegrant and a binder; and   the composition exhibits more than 80% of drug release within 30 minutes in 1000 ml of acetate buffer pH 4.5 using a USP II apparatus (Paddle) at a temperature of 37±0.5° C. and a rotation speed of 100 revolutions per minute.   
     
     
         2 . The high drug load immediate release solid oral pharmaceutical composition according to  claim 1 , wherein the composition is free of dry binder in the intragranular portion. 
     
     
         3 . The high drug load immediate release solid oral pharmaceutical composition according to  claim 1 , wherein the tablet is prepared by wet granulation process. 
     
     
         4 . The high drug load immediate release solid oral pharmaceutical composition according to  claim 1 , wherein the composition comprises eslicarbazepine acetate in an amount of from about 200 to about 800 mg. 
     
     
         5 . A method of treating epilepsy in a patient, wherein the method comprises administering to said patient the high drug load immediate release solid oral pharmaceutical composition according to  claim 1 . 
     
     
         6 . A method of treating partial onset seizure in a patient, wherein the method comprises administering to said patient the high drug load immediate release solid oral pharmaceutical composition according to  claim 1 . 
     
     
         7 . The high drug load immediate release solid oral pharmaceutical composition according to  claim 1 , wherein the disintegrant is selected from the group consisting of sodium starch glycolate, L-HPC, croscarmellose sodium, and crospovidone. 
     
     
         8 . The high drug load immediate release solid oral pharmaceutical composition according to  claim 1 , wherein the binder is selected from the group consisting of hydroxypropyl cellulose and hydroxypropyl methylcellulose. 
     
     
         9 . The high drug load immediate release solid oral pharmaceutical composition according to  claim 1 , wherein the lubricant consists of magnesium stearate. 
     
     
         10 . The high drug load immediate release solid oral pharmaceutical composition according to  claim 9 , wherein the magnesium stearate is present in an amount of between 0.5% and 1.0% w/w of the composition. 
     
     
         11 . The high drug load immediate release solid oral pharmaceutical composition according to  claim 1 , wherein the composition exhibits bioequivalence to a commercially available eslicarbazepine acetate tablet composition, when administered to the human subjects in fasting condition, wherein said bioequivalence is established by a 90% Confidence Interval for mean C max , AUC (0-t) , and AUC (0-∞)  which is between 80% and 125%. 
     
     
         12 . An immediate release solid oral pharmaceutical composition in the form of a tablet having an intragranular portion and an extragranular portion, wherein:
 the intragranular portion consists of eslicarbazepine acetate in an amount of 80% to 95% w/w of the composition, a binder being present in an amount of less than 3% w/w of the composition, and a disintegrant in an amount of between 0.1% and 12% w/w of the composition; and   the extragranular portion consists of a lubricant in an amount of between 0.5% and 5.0% w/w of the composition, wherein the disintegrant and the binder are present in the intragranular portion of the composition and the extragranular portion of the composition is free of a disintegrant and a binder.   
     
     
         13 . The immediate release solid oral pharmaceutical composition according to  claim 12 , wherein the composition is free of dry binder in the intragranular portion. 
     
     
         14 . The immediate release solid oral pharmaceutical composition according to  claim 12 , wherein the tablet is prepared by a wet granulation process. 
     
     
         15 . The immediate release solid oral pharmaceutical composition according to  claim 12 , wherein the disintegrant is selected from the group consisting of sodium starch glycolate, L-HPC, croscarmellose sodium, and crospovidone. 
     
     
         16 . The immediate release solid oral pharmaceutical composition according to  claim 12 , wherein the binder is selected from the group consisting of hydroxypropyl cellulose and hydroxypropyl methyl cellulose. 
     
     
         17 . The immediate release solid oral pharmaceutical composition according to  claim 12 , wherein the lubricant consists of magnesium stearate. 
     
     
         18 . The immediate release solid oral pharmaceutical composition according to  claim 12 , wherein the magnesium stearate is present in an amount of between 0.5% and 1.0% w/w of the composition. 
     
     
         19 . The immediate release solid oral pharmaceutical composition according to  claim 12 , wherein the composition comprises eslicarbazepine acetate ranges from about 200 to about 800 mg. 
     
     
         20 . A method of treating epilepsy and partial onset seizure in a patient, wherein the method comprises administering to said patient the high drug load immediate release solid oral pharmaceutical composition according to  claim 12 .