METHYLPHENIDATE COMPOSITIONS FOR TREATMENT OF ATTENTION DEFICIT HYPERACTIVITY DISORDER
A solid, oral pharmaceutical composition is described. The solid, oral pharmaceutical composition includes methylphenidate or a pharmaceutical salt thereof, wherein an in vivo absorption model of the solid, oral pharmaceutical composition has a function selected from the group consisting of: a single Weibull function, a double Weibull function, and a sigmoid eMax function. A correlation of a plurality of fractions of an in vitro dissolution of the solid, oral pharmaceutical composition with a same plurality of fractions of an in vivo absorption of the solid, oral pharmaceutical composition is non-linear. A method of treating a condition in a subject having a disorder or condition responsive to the administration of methylphenidate is also described. The method includes orally administering to the subject an effective amount of the solid, oral pharmaceutical composition.
1 - 54 . (canceled)
55 . A method of treating a subject having Attention Deficit Hyperactivity Disorder (ADHD) and an Autism Spectrum Disorder (ASD), the method comprising:
orally administering a composition comprising coated particles, said particles comprising:
a core comprising an effective amount of methylphenidate or a pharmaceutical salt thereof;
a sustained release layer enclosing the core; and
a delayed release layer enclosing the sustained release layer;
wherein the coated particles further comprise microcrystalline cellulose, dibutyl sebacate, diglycerides, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, magnesium stearate, methacrylic acid copolymer Type B, monoglycerides, polysorbate 80 and talc;
wherein the composition provides at least a 6 hour lag time during which the composition releases no more than 5% of the total methylphenidate hydrochloride followed by a sustained release period with a median T max of about 12-16 hours when administered to healthy adults; and
wherein the administering results in improvement in an ADHD-related behavioral impairment in a population of subjects having the ADHD and the ASD during a period of time.
56 . The method of claim 55 , wherein the ASD is autism.
57 . The method of claim 55 , wherein the improvement is measured by a validated rating scale, score or combined score.
58 . The method of claim 57 , wherein the validated rating scale, score or combined score is a Swanson, Kotkin, Agler, M-Flynn and Pelham (SKAMP) score, a SKAMP-CS combined score, an ADHD Rating Scale (ADHD-RS-IV) Total Score, a Before School Functioning Questionnaire (BSFQ) score, or Parent Rating of Evening and Morning Behavior-Revised (PREMB-R AM) score.
59 . The method of claim 58 , wherein efficacy of the improvement is measured by a fluctuation index (FI):
FI
=
[
maximum
(
CHP
)
-
minimum
(
CHP
)
]
average
(
CHP
)
wherein the CHP is a change in the SKAMP score in the population of subjects administered with the composition compared to a SKAMP score in a population of placebo-treated subjects having ADHD and ASD during the period of time.
60 . The method of claim 59 , wherein the fluctuation index (FI) has an absolute value less than 1.0.
61 . The method of claim 58 , wherein the value of the SKAMP scores do not change by more than, or than about, 6, 7, 8, 9, or 10 during the period of time.
62 . The method of claim 55 , wherein the period of time starts at 8, 9, 10, 11, 12, 13, 14, 15, or 16 hours after administration of the composition.
63 . The method of claim 62 , wherein the period of time ends at 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 hours after the start of the period of time.
64 . The method of claim 55 , wherein the period of time ends at 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 hours after the T max .
65 . The method of claim 55 , wherein the period of time ends when the subject falls asleep following the T max .
66 . The method of claim 55 , wherein the administering is in the evening.
67 . The method of claim 66 , wherein the period of time is from about 11 hours to about 23 hours after the administering in the evening.
68 . The method of claim 55 , wherein during the period of time, a rate of change of methylphenidate plasma concentration over time is not greater than +2.5 ng·hr/mL, wherein the effective amount is up to 100 mg.
69 . The method of claim 55 , wherein the period of time is between T max and 6 hours after T max , and the rate of change of methylphenidate plasma concentration is not less than −1.2 ng·hr/mL, wherein the effective amount is up to 100 mg.
70 . The method of claim 55 , wherein the period of time comprises a period wherein a methylphenidate plasma concentration is between C max and at least 40% C max and a rate of change of the methylphenidate plasma concentration is not greater than +1.5 ng·hr/mL and not less than −1.5 ng·hr/mL.
71 . The method of claim 55 , wherein the subject is a pediatric subject or an adolescent subject.
72 . The method of claim 55 , wherein the effective amount is 20 mg, 40 mg, 60 mg, 80 mg or 100 mg.
73 . The method of claim 55 , wherein the sustained release layer incompletely encloses the core.
74 . The method of claim 55 , wherein the delayed release layer incompletely encloses the sustained release layer or the core.