Modified release formulations containing drug-ion exchange resin complexes

Abstract

A particulate, modified release barrier coated drug-cation exchange resin complex comprising a core composed of a drug complexed with a pharmaceutically acceptable ion-exchange resin is provided. Methods of making and products containing this coated complex are described.

1 . An orally ingestible aqueous liquid suspension comprising:
 (A) barrier coated particulates which provide a modified release profile which comprise:
 (i) a particulate drug-cation exchange resin complex comprising at least one drug bound to a pharmaceutically acceptable water insoluble cation exchange resin, and further comprising a water insoluble polymer or copolymer, or hydrophilic polymer which forms a matrix with the drug-cation exchange resin complex, which particulate drug-cation exchange resin complex-(water insoluble polymer or copolymer or a hydrophilic polymer) matrix is capable of passing through a number 40 mesh screen, and 
 (ii) about 25% w/w to about 50% w/w of a water permeable, water insoluble, non-ionic, modified release polymeric diffusion barrier coating which provides a modified release profile to the drug in said drug-cation exchange resin complex-(water insoluble polymer or copolymer or hydrophilic polymer) matrix, wherein said at least one drug is methylphenidate, said barrier coating having an elongation factor of about 125% to about 400% and comprising a water insoluble polymer and about 2.5% w/w to about 20% w/w plasticizer based on the weight of the barrier coating; and 
   (B) at least one of (iiia) and/or (iiib):
 (iiia) an uncoated particulate methylphenidate-cation exchange resin complex of a size capable of passing through a number 40 mesh screen, wherein said uncoated methylphenidate-cation exchange resin complex is methylphenidate bound to a pharmaceutically acceptable water insoluble cation exchange resin and/or 
 (iiib) methylphenidate or a pharmaceutically acceptable salt thereof which is not complexed with an ion exchange resin; and 
   (C) a pharmaceutically acceptable aqueous suspension base, wherein said barrier coated drug-cation exchange resin complex-matrix as defined in (A) and said at least one additional component (B) are suspended in said base.   
     
     
         2 . The orally ingestible aqueous liquid suspension according to  claim 1 , wherein the water insoluble polymer or copolymer is present to form the drug-cation exchange resin complex-matrix as defined in (A). 
     
     
         3 . The orally ingestible aqueous liquid suspension according to  claim 1 , wherein the hydrophilic polymer is present to form the drug-cation exchange resin complex-matrix as defined in (A) and comprises a polyvinylpyrrolidone. 
     
     
         4 . The orally ingestible aqueous liquid suspension according to  claim 1 , wherein said water permeable, water insoluble, non-ionic polymeric diffusion barrier coating comprises about 30% to about 45% by weight of the drug-cation exchange resin complex. 
     
     
         5 . The orally ingestible aqueous liquid suspension according to  claim 1 , which comprises at least said uncoated particulate methylphenidate-cation exchange resin as defined in (B)(iiia). 
     
     
         6 . The orally ingestible aqueous liquid suspension according to  claim 5 , which comprises said methylphenidate or pharmaceutically acceptable salt thereof which is not complexed with an ion exchange resin as defined in (B)(iiib). 
     
     
         7 . The orally ingestible aqueous liquid suspension according to  claim 1  wherein said plasticizer comprises about 5% w/w to about 20% w/w of the coating. 
     
     
         8 . The orally ingestible aqueous liquid suspension according to  claim 1 , wherein said cation exchange resin used to form the complex as defined in (A) and/or B(iiia) is a sulfonated copolymer comprising styrene and a divinylbenzene. 
     
     
         9 . An orally ingestible aqueous liquid suspension comprising:
 (A) barrier coated particulates which provide a modified release profile for methylphenidate, which barrier coated particulates comprise:
 (i) a particulate drug-cation exchange resin complex comprising at least one drug bound to a pharmaceutically acceptable water insoluble cation exchange resin, and a water insoluble polymer or copolymer, or a hydrophilic polymer which forms a matrix with the drug-cation exchange resin complex, wherein the particulate drug-cation exchange resin complex-matrix is capable of passing through a number 40 mesh screen, and 
 (ii) about 25% w/w to about 50% w/w of a water permeable, water insoluble, non-ionic, modified release barrier coating which provides a modified release profile to the drug in said drug-cation exchange resin complex-(water insoluble polymer or copolymer or hydrophilic polymer) matrix, wherein said at least one drug is methylphenidate, said modified release barrier coating having an elongation factor of about 125% to about 400% and comprising a water insoluble polymer and a plasticizer in an amount of about 2% w/w to about 20% w/w of the barrier coating; and 
   (B) one or more of (iiia) and/or (iiib):
 (iiia) an uncoated particulate methylphenidate-cation exchange resin complex of a size capable of passing through a number 40 mesh screen, wherein said uncoated methylphenidate-cation exchange resin complex is methylphenidate bound to a pharmaceutically acceptable water insoluble cation exchange resin and/or 
 (iiib) methylphenidate or a pharmaceutically acceptable salt thereof which is not complexed with an ion exchange resin; and 
   (C) a pharmaceutically acceptable aqueous suspension base, wherein said barrier coated drug-cation exchange resin complex-matrix as defined in (A) and said at least one additional component (B) are suspended in said base.   
     
     
         10 . The orally ingestible aqueous liquid suspension according to  claim 9 , wherein the matrix comprises the hydrophilic polymer. 
     
     
         11 . The orally ingestible aqueous liquid suspension according to  claim 10 , wherein the hydrophilic polymer comprises polyvinylpyrrolidone. 
     
     
         12 . The orally ingestible aqueous liquid suspension according to  claim 9 . wherein said water permeable, water insoluble, non ionic polymeric diffusion barrier coating comprises about 30% to about 45% by weight of the drug-cation exchange resin complex. 
     
     
         13 . The orally ingestible aqueous liquid suspension according to  claim 9 , which comprises at least said uncoated particulate methylphenidate-cation exchange resin as defined in (B)(iiia). 
     
     
         14 . The orally ingestible aqueous liquid suspension according to  claim 13 , which comprises said methylphenidate or pharmaceutically acceptable salt thereof which is not complexed with an ion exchange resin as defined in (B)(iiib). 
     
     
         15 . The orally ingestible aqueous liquid suspension according to  claim 14 , wherein said cation exchange resin used to form the complex as defined in (A) and/or B(iiia) is a sulfonated copolymer comprising styrene and a divinylbenzene.