Formulation and process for drug loaded cores

Abstract

The present invention relates to a controlled release pellet of metoprolol and its pharmaceutically acceptable salts that uses a water soluble or a water swellable inert starting seed or core.

1 - 65 . (canceled) 
     
     
         66 . A controlled release metoprolol succinate tablet comprising:
 (a) 15-60 wt % based upon the total weight of the tablet of a plurality of controlled release metoprolol succinate pellets;   (b) 1-15 wt % based upon the total weight of the tablet of an immediate release dose of metoprolol succinate;   (c) 20-70 wt % based upon the total weight of the tablet of a disintegrant and/or cushioning agent; and   (d) 5-40 wt % based upon the total weight of the tablet of a lubricant,   wherein the tablet exhibits the following dissolution profile when tested in a USP Type 2 apparatus at 75 rpms, 37° C. in a phosphate buffer medium with a pH of 7.5:
 10-40% of the metoprolol is released after 2 hours; 
 20-50% of the metoprolol is released after 4 hours; 
 35-70% of the metoprolol is released after 8 hours; and 
 not less than 60% of the metoprolol is released after 16 hours. 
   
     
     
         67 . The controlled release tablet as defined in  claim 66  wherein the disintegrant and/or cushioning agent is selected from the group consisting of microcrystalline cellulose, lactose, crospovidone, sodium starch glycolate and mixtures thereof. 
     
     
         68 . The controlled release tablet as defined in  claim 66  wherein the lubricant is glyceryl monostearate. 
     
     
         69 . The controlled release tablet as defined in  claim 66  wherein the controlled release pellets pass through a 25 mesh screen and are retained on an 80 mesh screen. 
     
     
         70 . The controlled release tablet as defined in  claim 69  wherein the controlled release pellets comprise:
 (i) a water soluble inert core having a diameter of less than 30 mesh; 
 (ii) a drug layer applied to the inert core comprising: metoprolol succinate; a binder; and optionally a surfactant; and 
 (iii) a controlled release coating applied to the drug layer comprising a water insoluble film forming polymer. 
 
     
     
         71 . A controlled release metoprolol succinate tablet comprising:
 (a) 15-60 wt % based upon the total weight of the tablet of a plurality of controlled release metoprolol succinate pellets wherein the controlled release pellets pass through a 25 mesh screen and are retained on an 80 mesh screen and further comprise
 (i) a water soluble inert core having a diameter of less than 30 mesh; 
 (ii) a drug layer applied to the inert core comprising: metoprolol succinate; a binder selected from the group consisting of polyvinyl pyrrolidone, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyacrylate, ethylcellulose or mixture thereof; and optionally a surfactant; and 
 (iii) a controlled release coating applied to the drug layer comprising:
 50-95 wt % based upon the total weight of the controlled release coating of a water insoluble film forming polymer; 
 0-25 wt % based upon the total weight of the controlled release coating of an emulsifier; and 
 0-15 wt % based upon the total weight of the controlled release coating of a channeling agent; 
 
   (b) 1-15 wt % based upon the total weight of the tablet of an immediate release dose of metoprolol succinate;   (c) 20-70 wt % based upon the total weight of the tablet of a disintegrant and/or cushioning agent selected from the group consisting of microcrystalline cellulose, lactose, crospovidone, sodium starch glycolate and mixtures thereof; and   (d) 5-40 wt % based upon the total weight of the tablet of a lubricant,   wherein the tablet exhibits the following dissolution profile when tested in a USP Type 2 apparatus at 75 rpms, 37° C. in a phosphate buffer medium with a pH of 7.5:
 10-40% of the metoprolol is released after 2 hours; 
 20-50% of the metoprolol is released after 4 hours; 
 35-70% of the metoprolol is released after 8 hours; and 
 not less than 60% of the metoprolol is released after 16 hours.