Effective dosing of a child for the treatment of ADHD with methylphenidate
Inventors
Tengler, Mark • TEUSCHER, Nathan
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11166947-B2
Publication Date
2021-11-09
Expiration Date
Abstract
The present invention generally relates to treating attention-deficit disorders (e.g., ADHD) by providing an effective amount of an ADHD-effective agent to a patient in need thereof (e.g., a child).
Core Innovation
The invention relates to a method of treating an individual patient with attention deficit hyperactivity disorder (ADHD) by administering an oral dose form containing an ADHD-effective agent, where the oral dose form is characterized by defined in vitro dissolution release profiles and defined dissolution assay conditions. The dissolution assay uses an initial dissolution medium of 0.1 N HC1, and after 2 hours the medium is adjusted to a pH of about 6.8, and the dissolution assay is performed using a USP Apparatus 2.
For the oral dose form pharmacokinetics, at least one in vivo pharmacokinetic parameter selected from Cmax and multiple AUC ranges has a 90% confidence interval with upper and lower bounds within a range from 80%-125% of the value of the same parameter(s) for a bioequivalent reference composition. The oral dose form is a multi-component methylphenidate formulation including a sustained release racemic methylphenidate component comprising a water-insoluble, water permeable, pH-independent barrier coated, racemic methylphenidate-ion exchange resin complex in a polymeric matrix, with the barrier coating over the resin complex-matrix.
In addition to the sustained release component, the oral dose form comprises a first immediate release component comprising an immediate release uncoated racemic methylphenidate-ion exchange resin complex and a second immediate release racemic methylphenidate component comprising an uncomplexed racemic methylphenidate. The therapeutically effective amount of the oral dose form is correlated to the body weight of the individual patient using an explicit body weight range to methylphenidateHCl equivalent amount mapping.
Claims Coverage
The partial content provides one independent claim (clm-00001). It includes a single overall method framework combining in vitro dissolution release profile requirements under specified assay conditions, in vivo pharmacokinetic parameter confidence-interval bounds relative to a bioequivalent reference composition, a defined multi-component racemic methylphenidate oral dose form architecture, and a body-weight-correlated dosing amount mapping to methylphenidateHCl equivalent amounts.
In vitro dissolution release profile under specified assay conditions
The method administers an oral dose form whose in vitro profile releases 30-33% within the first 30 minutes, 34-42% within 2 hours, 40-80% within 4 hours, and 80-100% within 24 hours, using an initial dissolution medium of 0.1 N HC1 and adjusting to a pH of about 6.8 after 2 hours, with the dissolution assay performed using a USP Apparatus 2.
In vivo pharmacokinetic parameter confidence-interval within 80%-125% of a bioequivalent reference composition
For in vivo pharmacokinetic parameters of the oral dose form, at least one selected from Cmax and multiple AUC ranges has a 90% confidence interval with upper and lower bounds within 80%-125% of the value of the same parameter(s) for a bioequivalent reference composition.
Multi-component racemic methylphenidate oral dose form architecture
The oral dose form comprises a sustained release racemic methylphenidate component with a water-insoluble, water permeable, pH-independent barrier coated racemic methylphenidate-ion exchange resin complex in a polymeric matrix, a first immediate release component with an immediate release uncoated racemic methylphenidate-ion exchange resin complex, and a second immediate release racemic methylphenidate component with an uncomplexed racemic methylphenidate.
Body-weight-correlated therapeutically effective amount mapping to methylphenidateHCl equivalent
The therapeutically effective amount is correlated to the body weight of the individual patient using a body weight range mapping to methylphenidateHCl equivalent amounts.
The independent claim coverage centers on a combined specification that the administered ADHD oral dose form meets defined in vitro dissolution release profiles under USP Apparatus 2 with pH adjustment, that in vivo pharmacokinetic parameters have 90% confidence intervals bounded to 80%-125% versus a bioequivalent reference, that the formulation uses a sustained-release barrier-coated resin complex plus immediate-release components, and that the therapeutically effective amount is selected according to a body-weight-to-methylphenidateHCl equivalent dosing table.
Stated Advantages
Provides an oral dose form meeting defined in vitro dissolution release profiles and defined in vivo pharmacokinetic parameter behavior relative to a bioequivalent reference composition.
Enables selection of a therapeutically effective amount correlated to patient body weight using a body-weight-to-methylphenidateHCl equivalent mapping table.
Documented Applications
Treating an individual patient with attention deficit hyperactivity disorder (ADHD) by administering an oral dose form meeting the specified in vitro dissolution and in vivo pharmacokinetic confidence-interval criteria and selecting the dose based on body weight ranges.
Interested in licensing this patent?