Modified release formulations containing drug-ion exchange resin complexes
View Patent ↗A solid dose composition containing a mixture of a cured, modified release-barrier coated methylphenidate-ion exchange resin complex-matrix and an uncoated methylphenidate-ion exchange resin complex is described. The barrier coated methylphenidate-ion exchange resin complex-matrix comprises methylphenidate complexed with a pharmaceutically acceptable ion-exchange resin to form the complex which is admixed with a polymer to form a methylphenidate-ion exchange resin complex-matrix, which is subsequently coated with a modified release coating. The modified coating contains polyvinyl acetate polymer and a plasticizer and is cured.
1. A solid modified release methylphenidate tablet which provides at least about a 12 hour release profile and is suitable for oral ingestion which consists of methylphenidate particulates and pharmaceutically acceptable excipients compressed into a tablet, wherein said methylphenidate particulates comprise:
(A) a modified release methylphenidate component having a single active drug consisting of a methylphenidate, said component consisting of
(i) a particulate matrix comprising a particulate methylphenidate-ion exchange resin complex and a water insoluble polymer or copolymer, or hydrophilic polymer, said particulate matrix capable of passing through a number 40 mesh screen,
said methylphenidate-ion exchange resin complex comprising a pharmaceutically acceptable methylphenidate bound to a pharmaceutically acceptable water insoluble ion exchange resin to form said methylphenidate-ion exchange resin complex, said ion exchange resin being a sulfonated copolymer comprising styrene and divinylbenzene,
wherein said water insoluble polymer or copolymer, or hydrophilic polymer is present in an amount of about 3% to about 30% by weight, based on the weight of said methylphenidate-ion exchange resin complex,
(ii) a cured, high tensile strength, water permeable, water insoluble, non-ionic polymeric diffusion barrier coating over said particulate methylphenidate-ion exchange resin complex-water insoluble polymer or copolymer, or hydrophilic polymer matrix defined in (i), said cured barrier coating applied as an aqueous dispersion and comprising
(a) a polyvinylacetate polymer
(b) a stabilizer, and
(c) at least an amount of plasticizer effective to enhance the tensile strength of said cured barrier coating, whereby said barrier coating provides a modified release profile to said pharmaceutically acceptable methylphenidate in said methylphenidate-ion exchange resin complex-matrix and
(B) a particulate uncoated methylphenidate-ion exchange resin complex comprising a pharmaceutically acceptable methylphenidate as the sole active drug in the complex bound to a pharmaceutically acceptable water insoluble ion exchange resin to form said methylphenidate-ion exchange resin complex, said ion exchange resin being a sulfonated copolymer comprising styrene and divinylbenzene.
2. The composition according to claim 1 , wherein said ion exchange resin which is a sulfonated copolymer comprising styrene and divinylbenzene of (A) and (B) is an irregularly shaped particle.
3. The composition according to claim 1 , wherein said methylphenidate is dexmethylphenidate in (A) and/or (B).
4. The composition according to claim 1 , wherein said matrix comprises a water insoluble polymer or copolymer, or hydrophilic polymer in an amount of about 5 to about 20% by weight, based on the weight of said methylphenidate-ion exchange resin complex defined in (i).
5. The composition according to claim 1 wherein said cured high tensile strength, water permeable, water insoluble non-ionic polymeric diffusion barrier coating has an elongation factor of between about 125% and about 400%.
6. The composition according to claim 1 , wherein said methylphenidate-ion exchange resin complex-matrix includes a hydrophilic polymer.
7. The composition according to claim 6 , wherein said hydrophilic polymer comprises a polyvinylpyrrolidone.
8. The composition according to claim 1 , wherein said aqueous based coating dispersion comprises about 30% solids comprising polyvinylacetate with polyvinylpyrrolidone in a dry weight ratio about 10:1, respectively, and further includes an effective amount of a surfactant.
9. The composition according to claim 1 , wherein said methylphenidate-ion exchange resin complex-matrix comprises a water insoluble polymer or copolymer.
10. The composition according to claim 9 , wherein said methylphenidate-ion exchange resin complex-matrix comprises polyvinylacetate with a stabilizer comprising polyvinylpyrrolidone and an effective amount of a surfactant.
11. The composition according to claim 10 , wherein said water insoluble polymer is an aqueous dispersion comprising polyvinylacetate in an amount of about 27% w/w of the solids, polyvinylpyrrolidone in an amount of about 2.7% w/w of the solids, and sodium lauryl sulfate in an amount of about 0.3% w/w of the solids in the dispersion which is admixed with said methylphenidate-ion exchange resin complex to form said methylphenidate-ion exchange resin complex-matrix.
12. The composition according to claim 1 , wherein said plasticizer comprises about 5% to about 10% w/w of solids in said cured coating.
13. The composition according to claim 12 wherein said plasticizer comprises triacetin.
14. The composition according to claim 1 wherein said barrier coating further comprises a surfactant comprising sodium lauryl sulfate.
15. The composition according to claim 1 , wherein said cured, high tensile strength, water permeable, water insoluble, non ionic polymeric diffusion barrier coating comprises about 5% to about 200% by weight of the matrix defined in (i).
16. The composition according to claim 15 , wherein said cured, high tensile strength, water permeable, water insoluble, non ionic polymeric diffusion barrier coating comprises about 35% to about 50% by weight of the matrix defined in (i).
17. The composition according to claim 15 , wherein said cured, high tensile strength, water permeable, water insoluble, non ionic polymeric diffusion barrier coating comprises about 30% to about 45% by weight of the matrix defined in (i).
18. The composition according to claim 1 , wherein said cured, high tensile strength, water permeable, water insoluble, non ionic polymer diffusion barrier coating is cured for about 4 to about 16 hours.
19. The composition according to claim 18 , wherein said coating is cured for about 5 hours at about 50° C. to about 65° C.
20. The composition according to claim 19 , wherein said coating is cured at about 60° C.
21. The composition according to claim 1 , wherein said cured, high tensile strength, water permeable, water insoluble, non ionic polymeric diffusion barrier coating comprises 50% by weight of the matrix defined in (i).
22. The solid modified release methylphenidate tablet according to claim 1 , wherein said tablet further comprises a methylphenidate component which is not in a drug-ion exchange resin complex, in addition to said modified release methylphenidate component (A) and said uncoated methylphenidate-ion exchange resin complex (B).
23. The solid modified release methylphenidate tablet according to claim 1 , wherein said cured barrier coating comprises about 70% w/w to about 90% w/w polyvinylacetate, about 5% w/w to about 10% w/w polyvinylpyrrolidone, and about 2.5% to about 20% plasticizer w/w, based on the weight of the cured barrier coating layer.
24. The composition according to claim 11 , wherein said cured, high tensile strength, water permeable, water insoluble, non ionic polymeric diffusion barrier coating comprises about 25% to about 35% by weight of the methylphenidate-ion exchange resin complex-matrix defined in (i).