발생일자 2015.01.21 

사건번호 1:15-cv-00068 

법원국가 UNITED STATES OF AMERICA 

관할법원명 D.C.Delaware(지방법원) 

침해권리 특허 

원고명 Tris Pharma, Inc. ( 미국 / 외국기업 )  

피고명 Par Pharmaceutical, Inc./ Par Pharmaceutical Companies, Inc. ( 미국 / 외국기업 )  

소송유형 침해금지 

[Tris Pharma, Inc. v. Par Pharmaceutical, Inc. et al] 사건번호 1:15-cv-00068에 따르면 원고 Tris Pharma, Inc.는 피고 Par Pharmaceutical, Inc./ Par Pharmaceutical Companies, Inc.을 상대로 특허 US8062667, US8287903, US8465765, US8563033, US8778390을 침해하였다는 이유로 미국 델라웨어 지방법원에 소를 제기하였다. 

분쟁결과 분쟁중 

산업분류 화학∙바이오 > 의약품 

계쟁제품 "Methylphenidate hydrochloride 5mg/ml for extended release oral suspension", generic version of Quillivant XR

지재권번호/명칭

US8062667   Modified release formulations containing drug-ion exchange resin complexes 

 US8287903   Orally effective methylphenidate extended release powder and aqueous suspension product 

 US8465765   Orally effective methylphenidate extended release powder and aqueous suspension product 

 US8563033   Orally effective methylphenidate extended release powder and aqueous suspension product 

 US8778390   Orally effective methylphenidate extended release powder and aqueous suspension product 

A coated drug-ion exchange resin complex comprising a core composed of a drug complexed with a pharmaceutically acceptable ion-exchange resin is provided. The drug-ion exchange resin complex is in admixture with a release retardant. The coating is a polyvinyl acetate polymer and a plasticizer. Methods of making and products containing this coated complex are described. 

 1. An aqueous pharmaceutical suspension composition suitable for oral ingestion comprising: (i) a particulate matrix comprising a particulate drug-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 drug-ion exchange resin complex comprising a pharmaceutically acceptable drug bound to a pharmaceutically acceptable water insoluble ion exchange resin to form said drug-ion exchange resin complex, said ion exchange resin being selected from (A) a sulfonated copolymer comprising styrene and divinylbenzene, and (B) a copolymer comprising styrene and divinylbenzene having quaternary ammonium functional groups, 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 drug-ion exchange resin complex (ii) a cured, high tensile strength, water permeable, water insoluble, non-ionic polymeric diffusion barrier coating over said particulate drug-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 drug in said drug-ion exchange resin complex in said matrix and (iii) a pharmaceutically acceptable aqueous suspension base wherein said particulate drug-ion exchange resin complex and said water insoluble polymer or copolymer, or hydrophilic polymer covered with said cured barrier coating as defined in (ii) is suspended in said aqueous suspension base. 

 2. The aqueous suspension composition according to claim 1, wherein said water insoluble polymer or copolymer or the hydrophilic polymer-matrix is present in an amount of about 5 to about 20% by weight, based on the weight of said drug-ion exchange resin complex defined in (i). 

 3. The aqueous suspension composition according to claim 1 wherein said cured barrier coating has an elongation factor of between about 125% and about 400% when measured by a texture analyzer. 

 4. The aqueous suspension composition according to claim 1, wherein said ion exchange resin is a sulfonated copolymer comprising styrene and divinylbenzene. 

 5. The aqueous suspension composition according to claim 1, wherein said ion exchange resin is a copolymer comprising styrene and divinylbenzene having quaternary ammonium functional groups. 

 6. The aqueous suspension composition according to claim 1, further comprising an orally ingestible drug bound to a pharmaceutically acceptable, water insoluble ion exchange resin to form an uncoated particulate drug-ion exchange resin complex, said ion exchange resin in the uncoated complex being a sulfonated copolymer comprising styrene and divinylbenzene, and wherein said drug in said uncoated complex is either the same as or different from the pharmaceutically acceptable drug in (i) and said uncoated complex being of a size capable of passing through a number 40 mesh screen. 

 7. The aqueous suspension composition according to claim 6, wherein said drug in said uncoated drug-ion exchange resin complex is different from said pharmaceutically acceptable drug in (i). 

 8. The aqueous suspension composition according to claim 6, wherein said drug in said uncoated drug-ion exchange resin complex is the same as the pharmaceutically acceptable drug in (i). 

 9. The aqueous suspension composition according to claim 8, wherein said drug in said uncoated drug-ion exchange resin complex is a methylphenidate. 

 10. The aqueous suspension composition according to claim 1, further comprising a pharmaceutically acceptable drug in said pharmaceutically acceptable aqueous suspension base defined in (iii) being the same as or different from said pharmaceutically acceptable drug in (i). 

 11. The aqueous suspension composition according to claim 10, wherein said pharmaceutically acceptable drug in said suspension base is an antihistamine and is a different drug from said pharmaceutically acceptable drug in (i). 

 12. The aqueous suspension composition according to claim 11, wherein said antihistamine is fexofenadine or a pharmaceutically acceptable salt thereof. 

 13. The aqueous suspension composition according to claim 1, wherein said particulate matrix comprises said particulate drug-ion exchange resin complex and said hydrophilic polymer. 

 14. The aqueous suspension composition according to claim 13, wherein said hydrophilic polymer comprises a polyvinylpyrrolidone. 

 15. The aqueous suspension composition according to claim 1, wherein said cured barrier coating comprises polyvinyl acetate, polyvinylpyrrolidone and an effective amount of a surfactant, said polyvinylacetate and polyvinylpyrrolidone being in a dry weight ratio about 10:1. 

 16. The aqueous suspension composition according to claim 1, wherein said particulate matrix comprises said particulate drug-ion exchange resin complex and said water insoluble polymer or copolymer. 

 17. The aqueous suspension composition according to claim 16, wherein said water insoluble polymer in said particulate matrix comprises polyvinylacetate, wherein said particulate matrix comprises said particulate drug-ion exchange resin complex, a stabilizer comprising polyvinylpyrrolidone and an effective amount of a surfactant. 

 18. The aqueous suspension composition according to claim 17, said surfactant in said particulate matrix being sodium lauryl sulfate, wherein said particulate matrix is prepared by a process comprising mixing said particulate drug-ion exchange resin complex with an aqueous dispersion comprising said polyvinylacetate, said polyvinylpyrrolidone and said sodium lauryl sulfate to form a mass, drying said mass and milling through a 40 mesh screen, and wherein said polyvinylacetate is present in an amount of about 27% by weights of the said aqueous dispersion, said polyvinylpyrrolidone is present in an amount of about 2.7% by weight of said aqueous dispersion, and said sodium lauryl sulfate is present in an amount of about 0.3% by weight of the said aqueous dispersion which comprises 30% w/w solids. 

 19. The aqueous suspension composition according to claim 16, wherein said water insoluble polymer or copolymer comprises an acrylate polymer or copolymer. 

 20. The aqueous suspension composition according to claim 19, wherein said water insoluble copolymer comprises ethyl acrylate and methyl methacrylate. 

 21. The aqueous suspension composition according to claim 1 , wherein said plasticizer comprises about 5% to about 10% w/w of solids in said cured barrier coating. 

 22. The aqueous suspension composition according to claim 20 wherein said plasticizer comprises triacetin. 

 23. The aqueous suspension composition according to claim 1 wherein said cured barrier coating further comprises a surfactant comprising sodium lauryl sulfate. 

 24. The aqueous suspension composition according to claim 1, wherein said cured barrier coating comprises about 5% to about 200% by weight of the particulate drug-ion exchange resin complex defined in (i). 

 25. The aqueous suspension composition according to claim 24, wherein said cured barrier coating comprises about 35% to about 50% by weight of the particulate drug-ion exchange resin complex defined in (i). 

 26. The aqueous suspension composition according to claim 24, wherein said cured barrier coating comprises about 30% to about 45% by weight of the composition particulate drug-ion exchange resin complex defined in (i). 

 27. The aqueous suspension composition according to claim 1, wherein said cured barrier coating comprises 50% by weight of the particulate drug-ion exchange resin complex defined in (i). 

 28. The aqueous suspension composition according to claim 1, wherein said pharmaceutically acceptable drug in said particulate drug-ion exchange resin complex defined in (i) is selected from the group consisting of morphine, oxycodone, albuterol, methylphenidate, dexmethylphenidate, dextromethorphan, codeine, tramadol, pseudoephedrine, phenylephrine, hydrocodone, venlafaxine, ibuprofen, oxybutynin, clonidine, dexchlorpheniramine, fexofenadine, diphenhydramine, carbemazepine, oxymorphone, carbinoxamine, dicylomine, chlorpheniramine, amphetamine, naproxene, diclofenac, paroxetine, amoxicillin and pharmaceutically acceptable salts thereof. 

 29. The aqueous suspension composition according to claim 28, wherein said pharmaceutically acceptable drug in (i) is hydrocodone. 

 30. The aqueous suspension composition according to claim 28, wherein said pharmaceutically acceptable drug in (i) is clonidine. 

 31. The aqueous suspension composition according to claim 28, wherein said pharmaceutically acceptable drug in (i) is pseudoephedrine. 

 32. The aqueous suspension composition according to claim 1, wherein said pharmaceutically acceptable drug in (i) is selected from methylphenidate and dexmethylphenidate. 

 33. The aqueous suspension composition according to claim 1, wherein said pharmaceutically acceptable drug in (i) is carbinoxamine. 

 34. The aqueous suspension composition according to claim 28, wherein said pharmaceutically acceptable drug in (i) is diphenhydramine. 

 35. The aqueous suspension composition according to claim 28, wherein said pharmaceutically acceptable drug in (i) is ibuprofen. 

 36. The aqueous suspension composition according to claim 28, wherein said pharmaceutically acceptable drug in (i) is morphine. 

 37. An orally ingestible aqueous pharmaceutical suspension composition, comprising: (i) a particulate matrix comprising a particulate dextromethorphan-ion exchange resin complex, said dextromethorphan-ion exchange resin complex comprising dextromethorphan bound to a pharmaceutically acceptable water insoluble ion exchange resin, wherein said ion exchange resin is a sulfonated copolymer of styrene and divinylbenzene and wherein said matrix further comprises about 5% to about 20%, based on the weight of said dextromethorphan-ion exchange resin complex, of a water insoluble polymer or copolymer or a hydrophilic polymer, said particulate matrix comprising granules having a size capable of passing through a number 40 mesh screen; (ii) a cured high tensile strength, water permeable, water insoluble, non ionic polymeric diffusion barrier coating over said dextromethorphan-ion exchange resin complex and said water insoluble polymer or said hydrophilic polymer defined in (i), said cured barrier coating applied as an aqueous dispersion, and wherein said cured barrier coating comprises polyvinylacetate with a stabilizer comprising polyvinylpyrrolidone in a weight ratio of about 10:1, respectively, and said cured barrier coating further comprising from about 5% to about 10% by weight of a plasticizer based on the dry weight of said cured barrier coating, (iii) an uncoated particulate dextromethorphan-ion exchange resin complex wherein said ion exchange resin comprises a sulfonated copolymer of styrene and divinylbenzene and wherein said uncoated dextromethorphan-ion exchange resin complex comprises particles of a size capable of passing through a number 40 mesh screen; and (iv) a pharmaceutically acceptable aqueous suspension base, wherein said coated particulate dextromethorphan-ion exchange resin complex and said water insoluble polymer or said hydrophilic polymer defined in (ii) and said uncoated particulate dextromethorphan-ion exchange resin complex defined in (iii) are suspended in said base. 

 38. The aqueous pharmaceutical suspension composition according to claim 37, wherein said aqueous dispersion further comprises an effective amount of surfactant. 

 39. The aqueous pharmaceutical suspension composition according to claim 37, wherein said aqueous dispersion comprises polyvinylacetate in an amount of about 27% by weight polyvinylpyrrolidone in an amount of about 2.7% by weight, and sodium lauryl sulfate in an amount of about 0.3% by weight of the the aqueous dispersion which comprises 30% w/w solids. 

 40. The aqueous pharmaceutical suspension composition according to claim 37, wherein said plasticizer is triacetin. 

 41. The aqueous suspension composition according to claim 1, wherein said particulate matrix (i) comprises about 10% by weight to about 15% by weight of water insoluble polymer or copolymer. 

 42. The aqueous suspension composition according to claim 1, further comprising a second modified release diffusion barrier coated drug-ion exchange resin complex-matrix , wherein said second modified release diffusion barrier coated drug-in exchange resin complex-matrix contains a pharmaceutically acceptable drug which differs from the drug of said drug-ion exchange resin complex-matrix of (ii). 

 43. The aqueous suspension composition according to claim 1, wherein the cured barrier coating layer comprises at least about 75% w/w polyvinylacetate. 

 44. The aqueous suspension composition according to claim 1, wherein the cured barrier coating layer comprises about 75% to about 90% w/w polyvinylacetate. 

 45. The aqueous suspension composition according to claim 43, wherein the cured barrier coating layer comprises about 2.5% to about 20% by weight plasticizer. 

 46. The aqueous suspension composition according to claim 1, wherein the stabilizer is present in an amount of about 5 to about 10% w/w of the cured barrier coating layer. 

 47. The aqueous suspension composition according to claim 46, wherein the cured barrier coating further comprises a surfactant. 

 48. The aqueous pharmaceutical suspension composition suitable for oral ingestion according to claim 1, wherein said cured barrier coating comprises at least about 75% w/w polyvinylacetate, a stabilizer, and about 2.5% to about 20% w/w plasticizer based on the weight of said cured barrier coating. 

 49. The aqueous pharmaceutical suspension according to claim 48, wherein said barrier coating provides about 25% w/w to about 50% w/w weight gain to the particulate drug-ion exchange resin complex-matrix. 

 50. The aqueous pharmaceutical suspension according to claim 49, wherein said barrier coating provides about 30% w/w to about 45% w/w weight gain to the drug-ion exchange resin complex-matrix. 

 51. The aqueous pharmaceutical suspension according to claim 48, wherein the water insoluble polymer or copolymer, or hydrophilic polymer of said particulate matrix is present in an amount of about 5% w/w to about 20% w/w of the drug-ion exchange resin complex-matrix particles. 

 52. The aqueous pharmaceutical suspension according to claim 51, wherein the water insoluble polymer or copolymer, or hydrophilic polymer of said particulate matrix is present in an amount of about 10% w/w to about 15% w/w of the drug-ion exchange resin complex-matrix particles. 

 53. The aqueous pharmaceutical suspension according to claim 51, wherein the water insoluble polymer or copolymer, or hydrophilic polymer of said particulate matrix is present in an amount of about 10% w/w to about 15% w/w of the drug-ion exchange resin complex particles. 

 54. The aqueous pharmaceutical oral suspension according to claim 48, wherein the hydrophilic polymer of said particulate matrix is polyvinylpyrrolidone. 

 55. The aqueous pharmaceutical oral suspension according to claim 48, wherein said particulate matrix comprises polyvinylacetate, polyvinylpyrrolidone, and a surfactant. 

An oral methylphenidate powder which is reconstitutable into a final oral aqueous sustained release formulation containing at least about 50%, or at least about 80% by weight water based on the total weight of the suspension, is provided. The powder is a blend containing a combination of an uncoated methylphenidate-ion exchange resin complex, a barrier coated methylphenidate-ion exchange resin complex-matrix, and a water soluble buffering agent such that upon formed into an aqueous liquid formulation, the formulation has a pH in the range of about 3.5 to about 5, or about 4 to about 4.5. Following administration of a single dose of the oral aqueous methylphenidate suspension, a therapeutically effective amount of methylphenidate is reached in less than one hour and the composition provides a twelve-hour extended release profile. 

 1. A methylphenidate aqueous extended release oral suspension consisting of a combination of (a) a sustained release, cured, water-permeable, water-insoluble, non-ionic, polymeric diffusion barrier coated methylphenidate-ion exchange resin complex--matrix, wherein the cured diffusion barrier coating comprises about 70 to about 90% polyvinylacetate, about 2.5 to about 15% of a plasticizer, and a stabilizer, (b) an immediate release methylphenidate component, (c) at least 50% by weight water based on the total weight of the liquid component of the suspension, and (d) pharmaceutically acceptable excipients, wherein said suspension has a pH of about 3.5 to about 5, and said suspension providing a therapeutically effective plasma profile of d-methylphenidate for about 12 hours and a single mean plasma concentration peak for d-methylphenidate. 

 2. The methylphenidate aqueous extended release oral suspension according to claim 1, wherein said suspension has a pH in the range of about 4 to about 4.5. 

 3. The methylphenidate aqueous extended release oral suspension according to claim 1, wherein said suspension contains at least about 80% water by weight based on the total weight of the suspension. 

 4. The methylphenidate aqueous extended release oral suspension according to claim 1 wherein said suspension has a pharmacokinetic profile in which the single mean plasma concentration peak for d-methylphenidate has an area under the curve (AUC).sub.0-.infin. of about 114 ng-hr/mL to about 180 ng-hr/mL, C.sub.max of about 11 ng/mL to about 17 ng/mL, T.sub.max of about 4 hours to about 5.25 hours and T.sub.1/2 of about 5 hours to about 7 hours following a single oral administration of an aqueous suspension at a dose equivalent to 60 mg racemic methylphenidate HCl in adults. 

 5. The methylphenidate aqueous extended release oral suspension according to claim 4 wherein said suspension has a pharmacokinetic profile for d-methylphenidate having an AUC.sub.0-.infin. of about 143.65 ng-hr/mL, C.sub.max of about 13.61 ng/mL, T.sub.max of about 5 hours and T.sub.1/2 of about 5.65 hours following a single oral administration of an aqueous suspension at a dose equivalent to 60 mg racemic methylphenidate HCl in adults. 

 6. The methylphenidate aqueous extended release oral suspension according to claim 1 wherein said suspension has a pharmacokinetic profile in which the single mean plasma concentration peak for d-methylphenidate has an area under the curve (AUC).sub.0-.infin. of about 137.2 to about 214.4 ng-hr/mL, a C.sub.max of about 13.6 to about 21.3 ng/mL, and T.sub.max of about 3 to about 5 hours, following a single oral administration of an aqueous suspension at a dose equivalent to 72 mg racemic methylphenidate HCl in adults. 

 7. The methylphenidate aqueous extended release oral suspension according to claim 6 wherein said suspension has a pharmacokinetic profile for d-methylphenidate having an AUC.sub.0-.infin. of about 171.5 ng-hr/mL, a C.sub.max of about 17.0 ng/mL, and a T.sub.max of about 3.77 hours following a single oral administration of an aqueous liquid suspension at a dose equivalent to 72 mg racemic methylphenidate HCl in adults. 

 8. The methylphenidate aqueous extended release oral suspension according to claim 1, wherein said methylphenidate is selected from the group consisting of methylphenidate and dexmethylphenidate. 

 9. An aqueous methylphenidate extended release suspension having a pH in the range of about 4 to about 4.5 comprising at least about 80% water and a combination of (a) a sustained release, cured, water-permeable, water-insoluble, non-ionic, polymeric diffusion barrier coated methylphenidate-ion exchange resin complex-matrix, wherein the cured diffusion barrier coating comprises about 70 to about 90% polyvinylacetate, about 2.5 to about 15% of plasticizer, and a stabilizer, and said methylphenidate-ion exchange resin complex is in a matrix formed by granulating said complex with at least one hydrophilic or hydrophobic polymeric matrix forming component and (b) an immediate release uncoated methylphenidate-ion exchange resin complex, wherein the coated methylphenidate-ion exchange resin complex-matrix of (a) are particulates having an average size range of about 100 microns to about 250 microns, said suspension providing a single mean plasma concentration peak for d-methylphenidate and a therapeutically effective plasma profile of d-methylphenidate for about twelve hours. 

 10. A methylphenidate extended release powder blend, said extended release powder blend consisting of (i) an immediate release methylphenidate component; (ii) a cured water-permeable, high tensile strength, water insoluble, non-ionic, sustained release diffusion barrier coating comprising about 70 to about 90% polyvinylacetate polymer, about 2.5 to about 15% of a plasticizer, and a stabilizer over a methylphenidate--ion exchange resin complex-matrix; (iii) a water soluble buffering agent which adjusts the pH of an aqueous suspension formed by admixing said extended release powder blend with water to a pH in the range of about 3.5 to about 5; and (iv) optional pharmaceutical excipients, said powder blend providing a therapeutically effective plasma profile of d-methylphenidate for about 12 hours hours and a single mean plasma concentration peak for d-methylphenidate. 

 11. The methyphenidate extended release powder blend according to claim 10, wherein the immediate release methylphenidate component is an uncoated methylphenidate-ion exchange resin complex, optionally in a matrix with a hydrophilic or hydrophobic polymeric matrix forming component. 

 12. The methylphenidate extended release powder blend according to claim 11, wherein the cured barrier coating further comprises a surfactant. 

 13. The methylphenidate extended release powder blend according to claim 12, wherein the cured barrier coating further comprises about 5 to about 10% of the stabilizer, and about 0.1 to about 1% surfactant. 

 14. The methylphenidate extended release powder blend according to claim 12, wherein the plasticizer is triacetin and the surfactant is sodium lauryl sulfate. 

 15. The methylphenidate extended release powder blend according to claim 10, wherein the cured barrier coat is present in an amount which comprises about 20% to about 45% weight gain to the precoated methylphenidate-ion exchange resin complex-matrix. 

 16. The methylphenidate extended release powder blend according to claim 10, wherein the coated methylphenidate ion exchange resin complex-matrix comprises a hydrophilic polymer in an amount of about 5 to about 20% by weight, based on the weight of the precoated methylphenidate-ion exchange resin complex-matrix. 

 17. The methylphenidate extended release powder blend according to claim 16, wherein the hydrophilic polymer is polyvinylpyrrolidone. 

 18. The methylphenidate extended release powder blend according to claim 10, wherein the coated methylphenidate ion exchange resin complex-matrix comprises a hydrophobic polymer or co-polymer in an amount of about 5 to about 20% by weight, based on the weight of the precoated methylphenidate-ion exchange resin complex-matrix. 

 19. The methylphenidate extended release powder blend according to claim 10, wherein the extended release powder blend contains about 10 to about 30 parts by weight methylphenidate as provided in the immediate release component provided in (i) and about 70 to about 90 parts by weight methylphenidate as provided in the sustained release component provided in (ii), based upon the total weight of methylphenidate in the extended release powder blend. 

 20. The methylphenidate extended release powder blend according to claim 10, wherein said methylphenidate extended release powder blend further comprises water-soluble diluent granules which contain the buffering agent. 

 21. The methylphenidate extended release powder blend according to claim 20, wherein said buffering agent is selected from the group consisting of one or more of a pharmaceutically acceptable acid selected from the group consisting of citric acid, ascorbic acid, acetic acid, tartartic acid, phosphoric acid, a pharmaceutically acceptable salt of citric acid, ascorbic acid, acetic acid, tartartic acid, phosphoric acid, or a mixture of said pharmaceutically acceptable acid or salt. 

 22. The methylphenidate extended release powder blend according to claim 21, wherein said buffering agent is a mixture of sodium citrate and anhydrous citric acid. 

 23. The methylphenidate extended release powder blend according to claim 21, wherein the diluent granules further comprise one or more of a surfactant, a sweetener, and a preservative. 

 24. The methylphenidate extended release powder blend according to claim 23, wherein the surfactant in the diluent granules comprises a poloxamer. 

 25. The methylphenidate extended release powder blend according to claim 10, wherein said methylphenidate is selected from the group consisting of methylphenidate and dexmethylphenidate. 

 26. A solid dose unit in the form of a tablet or capsule comprising a methylphenidate extended release powder blend, said extended release powder blend comprising (i) an immediate release methylphenidate component and (ii) a cured, water-permeable, high tensile strength, water insoluble, non-ionic sustained release polymeric diffusion barrier coated methylphenidate-ion exchange resin complex-matrix, said cured diffusion barrier coating comprising about 70 to about 90% polyvinylacetate, about 2.5 to about 15% of a plasticizer, and a stabilizer, and being present in an amount of about 20% to about 45% weight gain to the methylphenidate-ion exchange resin complex-matrix based the weight of the matrix pre-coating, and wherein (i) and (ii) are provided in a ratio of about 10 to about 30 parts methylphenidate as provided in the immediate release component (i) to about 70 to about 90 parts by weight methylphenidate as provided in sustained release (ii), based on the total weight of methylphenidate in the extended release powder blend, said solid dose unit providing a single mean plasma concentration peak for d-methylphenidate and a therapeutically effective plasma profile of d-methylphenidate for about twelve hours. 

 27. The solid dose unit according to claim 26 having a pharmacokinetic profile in which the single mean plasma concentration for d-methylphenidate has an area under the curve (AUC).sub.0-.infin. of about 114 ng-hr/mL to about 180 ng-hr/mL, C.sub.max of about 11 ng/mL to about 17 ng/mL, T.sub.max of about 4 hours to about 5.25 hours and a T.sub.1/2 of about 5 hours to about 7 hours following a single oral administration at a dose equivalent to 60 mg racemic methylphenidate HCl in adults. 

 28. The solid dose unit according to claim 27 having a pharmacokinetic profile for d-methylphenidate having an AUC.sub.0-.infin. of about 143.65 ng-hr/mL, C.sub.max of about 13.61 ng/mL, T.sub.max of about 5 hours and T.sub.1/2 of about 5.65 hours following a single oral administration at a dose equivalent to 60 mg racemic methylphenidate HCl in adults. 

 29. The solid dose unit according to claim 26 having a pharmacokinetic profile for d-methylphenidate having an area under the curve (AUC).sub.0-.infin. of about 137.2 to about 214.4 ng-hr/mL, a C.sub.max of about 13.6 to about 21.3 ng/mL, and T.sub.max of about 3 to about 5 hours, following a single oral administration at a dose equivalent to 72 mg racemic methylphenidate HCl in adults. 

 30. The solid dose unit according to claim 29 having a pharmacokinetic profile in which methylphenidate has an AUC.sub.0-.infin. of about 171.5 ng-hr/mL, a C.sub.max of about 17.0 ng/mL, and a T.sub.max of about 3.77 hours following a single oral administration of an aqueous liquid suspension at a dose equivalent to 72 mg racemic methylphenidate HCl in adults. 

An oral methylphenidate powder which is reconstitutable into a final oral aqueous sustained release formulation containing at least about 50%, or at least about 80% by weight water based on the total weight of the suspension, is provided. The powder is a blend containing a combination of an uncoated methylphenidate-ion exchange resin complex, a barrier coated methylphenidate-ion exchange resin complex-matrix, and a water soluble buffering agent such that upon formed into an aqueous liquid formulation, the formulation has a pH in the range of about 3.5 to about 5, or about 4 to about 4.5. Following administration of a single dose of the oral aqueous methylphenidate suspension, a therapeutically effective amount of methylphenidate is reached in less than one hour and the composition provides a twelve-hour extended release profile. 

 1. A methylphenidate aqueous extended release oral suspension comprising (1) an immediate release methylphenidate component, (2) a sustained release methylphenidate component comprising a water-insoluble, water-permeable, pH-independent, barrier coated methylphenidate-ion exchange resin complex, and (3) water, wherein said suspension has a pH of about 3.5 to about 5 and said suspension provides a single mean average plasma concentration peak for methylphenidate and a therapeutically effective plasma profile for methylphenidate for about 12 hours. 

 2. The methylphenidate aqueous extended release oral suspension according to claim 1, wherein said suspension has a pH in the range of about 4 to about 4.5. 

 3. The suspension according to claim 1, wherein the barrier coating is selected from the group consisting of: (a) a cured water-permeable, high tensile strength, water insoluble, pH-independent barrier coating comprising a polyvinylacetate polymer and a plasticizer, (b) a barrier coating comprising an solvent-based ethylcellulose; and (c) a pH-independent acrylate based barrier coating comprising a methyl methyacrylate polymer or co-polymer. 

 4. The suspension according to claim 3, wherein the acrylate based barrier coating comprises a poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammonoethyl methacrylate chloride) polymer system. 

 5. The suspension according to claim 1, wherein the immediate release methylphenidate component is an uncoated methylphenidate-ion exchange resin complex, optionally in combination with a hydrophilic or hydrophobic polymeric matrix forming component. 

 6. The suspension according to claim 1, wherein the suspension has a pharmacokinetic profile in which the single mean plasma concentration peak for d-methylphenidate has an area under the curve (AUC).sub.0-.infin. of about 114 ng-hr/mL to about 180 ng-hr/mL, C.sub.max of about 11 ng/mL to about 17 ng/mL, T.sub.max of about 4 hours to about 5.25 hours and T.sub.1/2 of about 5 hours to about 7 hours following a single oral administration of an aqueous suspension at a dose equivalent to 60 mg racemic methylphenidate HCl in adults. 

 7. The methylphenidate aqueous extended release oral suspension according to claim 6 wherein the pharmacokinetic profile of d-methylphenidate has an AUC.sub.0-.infin. of about 143.65 ng-hr/mL, C.sub.max of about 13.61 ng/mL, T.sub.max of about 5 hours and T.sub.1/2 of about 5.65 hours following a single oral administration of an aqueous suspension at a dose equivalent to 60 mg racemic methylphenidate HCl in adults. 

 8. The suspension according to claim 1 wherein the suspension has a pharmacokinetic profile in which the single mean plasma concentration peak for methylphenidate has an area under the curve (AUC).sub.0-.infin. of about 137.2 to about 214.4 ng-hr/mL, a C.sub.max of about 13.6 to about 21.3 ng/mL, and T.sub.max of about 3 to about 5 hours, following a single oral administration of an aqueous suspension at a dose equivalent to 72 mg racemic methylphenidate HCl in adults. 

 9. The methylphenidate aqueous extended release oral suspension according to claim 8 wherein said suspension has a pharmacokinetic profile in which methylphenidate has an AUC.sub.0-.infin. of about 171.5 ng-hr/mL, a C.sub.max of about 17.0 ng/mL, and a T.sub.max of about 3.77 hours following a single oral administration of an aqueous suspension at a dose equivalent to 72 mg racemic methylphenidate HCl in adults. 

 10. The suspension according to claim 1, wherein the methylphenidate ion exchange resin complex is in a matrix with about 5 to about 20% by weight of a hydrophilic or hydrophobic polymeric matrix forming component, based on the weight of the uncoated methylphenidate-ion exchange resin complex-matrix. 

 11. The suspension according to claim 10, wherein the polymeric matrix forming component is a hydrophilic polymer comprising polyvinylpyrrolidone. 

 12. The suspension according to claim 10, wherein the polymeric matrix forming component is a hydrophobic polymer comprising polyvinylacetate. 

 13. The suspension according to claim 1, wherein said suspension contains at least about 80% of water by weight based on the total weight of the suspension. 

 14. The suspension according to claim 1, wherein said methylphenidate in the immediate release and/or sustained release component is independently selected from the group consisting of racemic methylphenidate and dexmethylphenidate. 

 15. The suspension according to claim 1, wherein the barrier coat comprises about 20% to about 45% by weight of the coated methylphenidate-ion exchange resin complex-matrix. 

 16. The suspension according to claim 1, wherein the suspension contains about 10 to about 30 parts by weight of methylphenidate as provided in the immediate release component and to about 70 to about 90 parts by weight of sustained release methylphenidate, based upon the total weight of methylphenidate in the suspension. 

 17. The suspension according to claim 1, further comprising a buffering agent selected from the group consisting of one or more of a pharmaceutically acceptable acid selected from the group consisting of citric acid, ascorbic acid, acetic acid, tartartic acid, phosphoric acid, a pharmaceutically acceptable salt of citric acid, ascorbic acid, acetic acid, tartartic acid, phosphoric acid, or a mixture of said pharmaceutically acceptable acid or salt, and mixtures thereof. 

 18. The suspension according to claim 17, wherein the buffering agent is a mixture of sodium citrate and anhydrous citric acid. 

 19. A method for treating a patient having a condition susceptible to treatment with methylphenidate, the method comprising administering to the patient a methylphenidate aqueous extended release oral suspension of claim 1, wherein said suspension provides a therapeutically effective amount of methylphenidate within 45 minutes after administering of said suspension and a single average plasma concentration peak. 

 20. The method according to claim 19, wherein the suspension which has a pH from about 4 to about 4.5. 

 21. A methylphenidate extended release powder blend, said extended release powder blend comprising: (i) an immediate release methylphenidate component; (ii) a sustained release water-insoluble, water-permeable, pH-independent, diffusion barrier coating over a methylphenidate-ion exchange resin complex-matrix; (iii) a water soluble buffering agent which adjusts the pH of an aqueous suspension formed by admixing said extended release powder blend with water to a pH in the range of about 3.5 to about 5; and (iv) optional pharmaceutical excipients, wherein said powder blend provides a therapeutically effective profile of d-methylphenidate for about 12 hours and a single mean plasma concentration peak for d-methylphenidate. 

 22. The powder blend according to claim 21, wherein the barrier coating is selected from the group consisting of: (a) a cured water-permeable, high tensile strength, water insoluble, barrier coating comprising a polyvinylacetate polymer and a plasticizer; (b) a barrier coating comprising a solvent-based ethylcellulose; and (c) a poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammoniumethylmethacrylate chloride) polymer. 

 23. The powder blend according to claim 21, wherein said methylphenidate extended release powder blend further comprises water-soluble diluent granules which contain the buffering agent. 

 24. The powder blend according to claim 23, wherein the diluent granules further comprise one or more of a surfactant, a sweetener, and a preservative. 

 25. The powder blend according to claim 24, wherein the surfactant in the diluent granules comprises a poloxamer. 

 26. The powder blend according to claim 21, wherein said buffering agent is selected from the group consisting of one or more of a pharmaceutically acceptable acid selected from the group consisting of citric acid, ascorbic acid, acetic acid, tartartic acid, phosphoric acid, a pharmaceutically acceptable salt of citric acid, ascorbic acid, acetic acid, tartartic acid, phosphoric acid, or a mixture of said pharmaceutically acceptable acid or salt. 

 27. A tablet or capsule comprising the powder blend according to claim 21. 

 28. The methylphenidate aqueous extended release oral suspension according to claim 1 which has a stable shelf-life under ambient conditions over a period of at least about four months at room temperature. 

 29. The methylphenidate aqueous extended release oral suspension according to claim 28, which has less than about 5% loss in potency over a period of at least about 4 months of storage at room temperature. 

 30. The methylphenidate aqueous extended release oral suspension according to claim 29, which has less than about 3% loss in potency over a period of at least about 4 months of storage at room temperature.