Oral Pharmaceutical Dosage Forms

Abstract

Controlled release oral dosage forms suitable for administration of methylphenidate are provided. Abuse-resistant controlled release oral dosage forms suitable for administration of methylphenidate are also provided. Methods of treating ADD and ADHD using the oral dosage forms are also provided.

1 . An oral controlled release dosage form comprising a formulation comprising:
 methylphenidate at about 1 to about 40 wt % relative to the total weight of the formulation;   a high viscosity liquid carrier material (HVLCM) at about 30 to 60 wt % relative to the total weight of the formulation;   a rheology modifier at about 1 to 18 wt % relative to the total weight of the formulation;   a network former at about 2 to 10 wt % relative to the total weight of the formulation;   a solvent at about 1 to 35 wt % relative to the total weight of the formulation; and   a viscosity enhancing agent at about 0.1 to 6 wt % relative to the total weight of the formulation,   
       wherein said dosage form is characterized by providing:
 (i) an initial increasing in vivo rate of release of methylphenidate from the controlled release system suitable to provide an initial increasing-rate phase of less than or equal to about 2 hours, and sufficient to provide a therapeutically effective amount of methylphenidate for a rapid onset of action; and 
 (ii) a second, non-ascending in vivo rate of release of methylphenidate from the controlled release system that provides a subsequent non-ascending phase sufficient to provide a therapeutically effective amount of methylphenidate through at least about 11 to 12 hours post administration. 
 
     
     
         2 . The controlled release oral dosage form of  claim 1 , wherein the initial increasing-rate phase is sufficient to provide an onset of action within about 1 hour post administration. 
     
     
         3 . (canceled) 
     
     
         4 . The controlled release oral dosage form of  claim 1 , wherein the subsequent non-ascending phase is sufficient to provide a therapeutically effective amount of methylphenidate through at least 14 hours post administration 
     
     
         5 .- 8 . (canceled) 
     
     
         9 . The controlled release oral dosage form of  claim 1 , wherein the dosage form is abuse-resistant. 
     
     
         10 . The abuse-resistant controlled release oral dosage form of  claim 9 , wherein the formulation provides a decreased risk of misuse or abuse. 
     
     
         11 . The abuse-resistant controlled release oral dosage form of  claim 10 , wherein said decreased risk of misuse or abuse is characterized by a low in vitro solvent extractability value of the methylphenidate from the dosage form, wherein less than 45% of the methylphenidate is extracted after 60 min of extraction in 40% ethanol at 25° C. 
     
     
         12 . The abuse-resistant controlled release oral dosage form of  claim 10 , wherein said decreased risk of misuse or abuse is characterized by the absence of any significant effect on absorption of the methylphenidate from the dosage form upon co-ingestion of the dosage form and alcohol by a subject wherein both the C max  ratio and the AUC ratio of absorption of the methylphenidate from the dosage form when taken with water or with 40% ethanol is within a range of about 0.8 to 1.2. 
     
     
         13 . The abuse-resistant controlled release oral dosage form of  claim 10 , wherein said decreased risk of misuse or abuse is characterized by a low injectability potential, wherein the force required to inject 1 gram of the formulation from a 3 ml syringe through an 18 G needle exceeds 62 N at a crosshead speed of 150 mm/min at 25° C. 
     
     
         14 . The abuse-resistant controlled release oral dosage form of  claim 9 , wherein said dosage form is not susceptible to common forms of abuse comprising injection, inhalation and volatilization. 
     
     
         15 .- 16 . (canceled) 
     
     
         17 . A method of treating Attention Deficit Disorder (ADD) or Attention Deficit Hyperactivity Disorder (ADHD) in a subject, said method comprising administering the controlled release oral dosage form of  claim 1  to the subject on a once-day (QD) basis. 
     
     
         18 .- 26 . (canceled) 
     
     
         27 . The controlled release oral dosage form of  claim 1 , wherein the formulation further comprises a surfactant. 
     
     
         28 .- 29 . (canceled) 
     
     
         30 . The controlled release oral dosage form of  claim 1 , wherein the viscosity enhancing agent comprises a stiffening agent. 
     
     
         31 . The controlled release oral dosage form of  claim 30 , wherein the viscosity enhancing agent comprises a SiO 2 . 
     
     
         32 . The controlled release oral dosage form of  claim 1 , wherein the solvent comprises triacetin. 
     
     
         33 .- 44 . (canceled) 
     
     
         45 . The controlled release oral dosage form of  claim 1 , wherein the HVLCM is sucrose acetate isobutyrate (SAIB). 
     
     
         46 .- 48 . (canceled) 
     
     
         49 . The controlled release oral dosage form of  claim 1 , wherein the network former is cellulose acetate butyrate (CAB). 
     
     
         50 . The controlled release oral dosage form of  claim 1 , wherein the rheology modifier is isopropyl myristate (IPM). 
     
     
         51 .- 57 . (canceled)