Nova Patents
IL227734A

Extended release powder and aqueous suspension comprising methylphenidate

Abstract

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IL227734A, drawing sheet 1
Sheet 1 of 5

Term

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  1. Priority
  2. Filed
  3. Published
  4. Today

9 claims: 4 independent, 5 dependent

  1. 1
    227734/4 What is claimed is:1. A methylphenidate aqueous extended release oral suspension comprising at least 50% byweight water based on the total weight of the liquid component of the suspension, an immediaterelease methylphenidate component, and a sustained release methylphenidate component, whereinsaid sustained release methylphenidate component comprises a methylphenidate - ion exchange resincomplex and a sustained release barrier coating over the complex, said suspension having a pH ofabout 3.5 to about 5. 2. The methylphenidate aqueous extended release oral suspension according to claim 1, whereinsaid suspension has a pH in the range of 4 to-4.5. 3. The methylphenidate aqueous extended release oral suspension according to claim 1 whereinsaid suspension has a pharmacokinetic profile in which d-methylphenidate has an AUCo-® of about114 ng-hr/mL to about 180 ng-hr/mL, Cmax of about 11 ng/mL to about 17 ng/mL, Tmax of about 4hours to about 5.25 hours and T1/2 of about 5 hours to about 7 hours following a single oraladministration of an aqueous liquid suspension at a dose equivalent to 60 mg racemic MPH in adults;preferably wherein said suspension has a pharmacokinetic profile of Figure 3 in whichd-methylphenidate has an AUC0-/ of about 143.65 ng-hr/mL, Cmax of about 13.61 ng/mL, Tmax ofabout 5 hours and T1/2 of about 5.65 hours following a single oral administration of an aqueous liquidsuspension at a dose equivalent to 60 mg racemic MPH in adults. 4. The methylphenidate aqueous extended release oral suspension according to claim 1 whereinsaid suspension has a pharmacokinetic profile in which methylphenidate has an AUCo-® of about137.2 to about 214.4 ng-hr/mL and a Cmax of about 13.6 to about 21.3 ng/mL, and Tmax of about 3 toabout 5 hours, following a single oral administration of an aqueous liquid suspension at a doseequivalent to 72 mg racemic MPH in adults;preferably wherein said suspension has apharmacokinetic profile of Figure 1 in which d-methylphenidate has an AUCo-® of about 171.5 ng-hr/mL and a Cmax of about 17.0 ng/mL, and a Tmax of about 3.77 hours following a single oraladministration of an aqueous liquid suspension at a dose equivalent to 72 mg racemic MPH in adults. 5. A methylphenidate extended release powder blend, said extended release powder blendcomprising (i) an immediate release methylphenidate component and (ii) a sustained release barrier 62 227734/4coated methylphenidate - ion exchange resin complex - matrix, and (iii) a water soluble bufferingagent;, which adjusts the pH of an aqueous suspension formed by admixing said extended releasepowder blend with water to a pH of 3.5 to 5.
  2. 5
    27. An aqueous methylphenidate extended release suspension having a pH in the range of about 4 to about 4.5 comprising at least about 80 percent water and a combination of (a) a sustainedrelease, cured, water-permeable, water-insoluble, non-ionic, polymeric diffusion barrier coatedmethylphenidate-ion exchange resin complex-matrix, wherein the cured diffusion barrier coatingcomprises about 70 to about 90 percent polyvinylacetate, about 2.5 to about 15 percent of plasticizer,and a stabilizer, and said methylphenidate-ion exchange resin complex is in a matrix formed bygranulating said complex with at least one hydrophilic or hydrophobic polymeric matrix formingcomponent and (b) an immediate release uncoated methylphenidate-ion exchange resin complex,wherein the coated methylphenidate-ion exchange resin complex-matrix of (a) are particulates havingan average size range of about 100 microns to about 250 microns, said suspension providing a singlemean plasma concentration peak for d-methylphenidate and a therapeutically effective plasma profileof d-methylphenidate for about twelve hours.
  3. 6
    28. A methylphenidate extended release powder blend, said extended release powder blendconsisting of (i) an immediate release methylphenidate component;(ii) a cured water-permeable,high tensile strength, water insoluble, non-ionic, sustained release diffusion barrier coatingcomprising about 70 to about 90 percent polyvinylacetate polymer, about 2.5 to about 15 percent of aplasticizer, and a stabilizer over a methylphenidate-ion exchange resin complex-matrix;(iii) a watersoluble buffering agent which adjusts the pH of an aqueous suspension formed by admixing saidextended 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 plasmaprofile of d-methylphenidate for about 12 hours and a single mean plasma concentration peak ford-methylphenidate. 29. A solid dose unit in the form of a tablet or capsule comprising a methylphenidate extendedrelease powder blend, said extended release powder blend comprising (i) an immediate releasemethylphenidate component and (ii) a cured, water-permeable, high tensile strength, water insoluble,non-ionic sustained release polymeric diffusion barrier coated methylphenidate-ion exchange resincomplex-matrix, said cured diffusion barrier coating comprising about 70 to about 90 percent 67 227734/4polyvinylacetate, about 2.5 to about 15 percent of a plasticizer, and a stabilizer, and being present inan amount of about 20 percent to about 45 percent weight gain to the methylphenidate-ion exchangeresin complex-matrix based the weight of the matrix pre-coating, and wherein (i) and (ii) areprovided in a ratio of about 10 to about 30 parts methylphenidate as provided in the immediaterelease component (i) to about 70 to about 90 parts by weight methylphenidate as provided insustained release (ii), based on the total weight of methylphenidate in the extended release powderblend, said solid dose unit providing a single mean plasma concentration peak for d-methylphenidateand a therapeutically effective plasma profile of d-methylphenidate for about twelve hours.
  4. 9
    46. A powder which when admixed with water forms an aqueous oral suspension, said powdercomprising (i) an immediate release methylphenidate component, (ii) a sustained release water-insoluble, water-permeable, pH-independent, barrier coated methylphenidate-ion exchange resincomplex, and (iii) a buffering agent which adjusts the pH of the oral aqueous suspension comprisingthe powder to a pH of about 4.2, wherein the oral aqueous suspension comprising the powder furthercomprises at least about 80 percent of water based on the total weight of the suspension, wherein theoral aqueous suspension has less than about 1 percent of threo-a-phenyl-2-piperidineacetic acidhydrochloride impurity after a period of about 1 month of storage at room temperature, and whereinfollowing a single oral administration of the aqueous oral suspension to adult subjects under fastedconditions, at a dose equivalent to 60 mg racemic methylphenidate HC1, the oral aqueous suspensionhas a pharmacokinetic profile in which d-methylphenidate has an area under the curve (AUC)o-s ofabout 114 ng-hr/mL to about 180 ng-hr/mL in adults under fasted conditions, a Cmaxof about 11ng/mL to about 17 ng/mL in adults, and wherein following a single administration of the aqueousoral suspension to adult, the d-methylphenidate has a reduced Tmaxin adults subjects fed with a high-fat meal prior to administration compared to adult subjects in a fasted state prior to administration. For the Applicants, REINHOLD COHN AND PARTNERS By:72
Independent claims4