MODIFIED RELEASE FORMULATIONS CONTAINING DRUG - ION EXCHANGE RESIN COMPLEXES
A particulate, pH-independent, 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 solid dose composition comprising:
(A) barrier coated particulates which provide a modified release profile which comprises:
(i) a particulate drug-cation exchange resin complex comprising at least one drug bound to a pharmaceutically acceptable water insoluble cation exchange resin, and optionally 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-(optional 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 high tensile strength, 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-(optional water insoluble polymer or copolymer or hydrophilic polymer) matrix, said barrier coating having an elongation factor of about 125% to about 400%, wherein said at least one drug is methylphenidate; and
(B) at least one additional component selected from:
(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.
2 . The orally ingestible solid dose composition 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 solid dose composition 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 solid dose composition according to claim 1 , wherein said high tensile strength, 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 solid dose composition according to claim 1 , which comprises at least said uncoated particulate methylphenidate-cation exchange resin as defined in (B)(iiia).
6 . The orally ingestible solid dose composition 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 solid dose composition according to claim 1 wherein said high tensile strength, water permeable, water insoluble non-ionic polymeric diffusion barrier coating further comprises a plasticizer in an amount of about 2% w/w to about 20% w/w of the coating layer.
8 . The orally ingestible solid dose composition according to claim 1 wherein said plasticizer comprises about 5% w/w to about 20% w/w of the coating.
9 . The orally ingestible solid dose composition 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.
10 . The orally ingestible solid dose composition according to claim 1 , wherein said composition is a tablet.
11 . An orally ingestible solid dose tablet comprising:
(A) barrier coated particulates which provide about an eight hour modified release profile which comprises:
(i) a particulate drug-cation exchange resin complex comprising at least one drug bound to a pharmaceutically acceptable water insoluble cation exchange resin, and optionally 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-(optional 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 high tensile strength, 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-(optional water insoluble polymer or copolymer or hydrophilic polymer) matrix, said barrier coating having an elongation factor of about 125% to about 400%, wherein said at least one drug is methylphenidate; and
(B) at least one additional component selected from:
(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.
12 . The orally ingestible solid dose tablet according to claim 11 , wherein the matrix is present and comprises the hydrophilic polymer.
13 . The orally ingestible solid dose tablet according to claim 12 , wherein the hydrophilic polymer comprises polyvinylpyrrolidone.
14 . The orally ingestible solid dose tablet according to claim 11 , wherein the water insoluble polymer or copolymer is present to form the drug-cation exchange resin complex-matrix as defined in (A).
15 . The orally ingestible solid dose tablet according to claim 11 , wherein said high tensile strength, 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.
16 . The orally ingestible solid dose tablet according to claim 11 , which comprises at least said uncoated particulate methylphenidate-cation exchange resin as defined in (B)(iiia).
17 . The orally ingestible solid dose tablet according to claim 16 , which comprises said methylphenidate or pharmaceutically acceptable salt thereof which is not complexed with an ion exchange resin as defined in (B)(iiib).
18 . The orally ingestible solid dose tablet according to claim 11 wherein said high tensile strength, water permeable, water insoluble non-ionic polymeric diffusion barrier coating further comprises a plasticizer in an amount of about 2% w/w to about 20% w/w of the coating layer.
19 . The orally ingestible solid dose tablet according to claim 11 wherein said plasticizer comprises about 5% w/w to about 20% w/w of the coating.
20 . The orally ingestible solid dose tablet according to claim 11 , 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.