MODIFIED RELEASE FORMULATIONS CONTAINING DRUG-ION EXCHANGE RESIN COMPLEXES

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 the weight percentage of said modified release barrier coating is based on the weight of drug-cation exchange complex-matrix without said barrier coating, 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 the weight percentage of said modified release barrier coating is based on the weight of drug-cation exchange complex-matrix without said modified release barrier coating, 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.