Compositions for treatment of attention deficit hyperactivity disorder
Therapeutic compositions deliver a therapeutic amount of methylphenidate in a delayed and extended release formulation. The dosage form exhibits a lag time prior to release of from 6 to 8 hours or longer, followed by a sustained release period.
1. A solid, oral pharmaceutical composition comprising: coated particles comprising:
a core comprising methylphenidate hydrochloride;
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; and
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.
2. The composition of claim 1 , wherein the composition provides at least an 8 hour lag time during which the composition releases no more than about 5% of the total methylphenidate hydrochloride.
3. The composition of claim 1 , wherein the composition provides at least a 10 hour lag time during which the composition releases no more than 10% of the total methylphenidate hydrochloride.
4. The solid, oral pharmaceutical composition of claim 1 , wherein the composition is contained in a capsule comprising hydroxypropyl methylcellulose.
5. The solid, oral pharmaceutical composition of claim 1 , wherein the composition provides pediatric or adolescent subjects having Attention Deficit Hyperactivity Disorder (ADHD) with a significant improvement compared to a placebo in Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale (SKAMP) combined scores for a period from about 11 hours through about 23 hours after administration in the evening.
6. The solid, oral pharmaceutical composition of claim 1 , wherein the composition provides pediatric or adolescent subjects having Attention Deficit Hyperactivity Disorder (ADHD) with a significant improvement compared to a placebo in ADHD Rating Scale (ADHD-RS-IV) Total Score, Before School Functioning Questionnaire (BSFQ) score, and/or Parent Rating of Evening and Morning Behavior-Revised (PREMB-R AM) score when administered in the evening.
7. The solid, oral pharmaceutical composition of claim 1 , wherein the composition comprises 20 mg, 40 mg, 60 mg, 80 mg or 100 mg of methylphenidate hydrochloride.
8. A solid, oral pharmaceutical composition comprising: coated particles consisting of:
a core comprising methylphenidate hydrochloride;
a sustained release layer enclosing the core; and
a delayed release layer enclosing the sustained release layer;
wherein the coated particles further consist of microcrystalline cellulose, dibutyl sebacate, diglycerides, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, magnesium stearate, methacrylic acid copolymer Type B, monoglycerides, polysorbate 80 and talc; and
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.
9. The composition of claim 8 , wherein the composition provides at least an 8 hour lag time during which the composition releases no more than about 5% of the total methylphenidate hydrochloride.
10. The composition of claim 8 , wherein the composition provides at least a 10 hour lag time during which the composition releases no more than 10% of the total methylphenidate hydrochloride.
11. The solid, oral pharmaceutical composition of claim 8 , wherein the composition is contained in a capsule comprising hydroxypropyl methylcellulose.
12. The solid, oral pharmaceutical composition of claim 8 , wherein the composition provides a pediatric or adolescent subjects having Attention Deficit Hyperactivity Disorder (ADHD) with a significant improvement compared to a placebo in Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale (SKAMP) combined scores for a period from about 11 hours through about 23 hours after administration in the evening.
13. The solid, oral pharmaceutical composition of claim 8 , wherein the composition provides pediatric or adolescent subjects having Attention Deficit Hyperactivity Disorder (ADHD) with a significant improvement compared to a placebo in ADHD Rating Scale (ADHD-RS-IV) Total Score, Before School Functioning Questionnaire (BSFQ) score, and/or Parent Rating of Evening and Morning Behavior-Revised (PREMB-R AM) score when administered in the evening.
14. The solid, oral pharmaceutical composition of claim 8 , wherein the composition comprises 20 mg, 40 mg, 60 mg, 80 mg or 100 mg of methylphenidate hydrochloride.