Abuse deterrent and anti-dose dumping pharmaceutical salts useful for the treatment of attention deficit/hyperactivity disorder

摘要

A pharmaceutical composition comprising a drug substance consisting essentially of a pharmaceutically acceptable organic acid addition salt of an amine containing pharmaceutically active compound wherein the amine containing pharmaceutical active compound is selected from the group consisting of racemic or single isomer ritalinic acid or phenethylamine derivatives and the drug substance has a physical form selected from amorphous and polymorphic.

主权项

1. A method for treating Attention Deficit/Hyperactivity Disorder comprising:
administering a first drug product comprising a first drug substance wherein said first drug substance comprises a first amine containing pharmaceutically active compound selected from the group consisting of methyl phenidate, amphetamine and imipramine and said first drug substance is at a first dose to reach a first therapeutic level of said first drug substance wherein said first drug substance has an immediate release profile of said first amine containing pharmaceutically active compound from said first drug substance wherein said immediate release profile is defined as at least 85% release within 30 minutes at gastric conditions; monitoring results of said first dose to determine second dose; administering a second drug product comprising said first drug substance at said second dose to reach a second therapeutic level wherein said second drug substance comprises said first amine containing pharmaceutically active compound with said immediate release profile; monitoring results of said second dose to confirm suitability of said second dose; administering a third drug product comprising a second drug substance wherein said second drug substance has a release profile which is slower than said immediate release profile and said slower release profile is suitable for maintaining said therapeutic level and said second drug substance is selected from the group consisting of: amorphous racemic-methylphenidate pamoate characterized by at least one method selected from the group consisting of:
an endothermic phase change of at least 70 J/gram at greater than 200° C.; anda PXRD diffractogram of FIG. 3; polymorphic racemic-methylphenidate stearylamine pamoate characterized by at least one method selected from the group consisting of:
an endothermic phase change of at least 15 J/g at a temperature above 50° C.; an endothermic phase change of at least 10 J/g at a temperature of above 90° C.; an endothermic phase change of at least 2 J/g at a temperature above 105° C.; an endothermic phase change of at least 4 J/g at above 155° C. and an endothermic phase change of at least 20 J/g above 180° C.; anda PXRD diffractogram of FIG. 48; amorphous d-methylphenidate pamoate characterized by at least one method selected from the group consisting of:
an endothermic phase change of at least 45 J/gram at greater than 70° C. and an endothermic phase change of at least 30 J/gram at greater than 180° C.; anda PXRD diffractogram of FIG. 12; polymorphic d-methylphenidate pamoate characterized by at least one method selected from the group consisting of:
an endothermic phase change of at least 35 J/gram at greater than 185° C.; anda PXRD diffractogram of FIG. 15; polymorphic racemic-methylphenidate pamoate characterized by at least one method selected from the group consisting of:
an endothermic phase change of at least 75 J/gram at greater than 200° C.; anda PXRD diffractogram of FIG. 6; amorphous dextro-amphetamine pamoate characterized by at least one method selected from the group consisting of:
endothermic phase change of at least 10 J/gram at greater than 200° C. and an endothermic phase change of at least 75 J/gram at greater than 220° C.; anda PXRD diffractogram of FIG. 21; polymorphic dextro-amphetamine pamoate characterized by at least one method selected from the group consisting of:
an endothermic phase change of at least 60 J/gram at greater than 200° C.; anda PXRD diffractogram of FIG. 24; amorphous d-methylphenidate mono-triethylammonium pamoate characterized by at least one method selected from the group consisting of:
an endothermic phase change of at least 12 J/g at a temperature above 240° C.; anda PXRD diffractogram of FIG. 52; amorphous imipramine mono-triethylammonium pamoate characterized by an PXRD diffractogram of FIG. 60; polymorphic imipramine stearylamine pamoate characterized by at least one method selected from the group consisting of:
an endothermic phase change of at least 40 J/g at a temperature above 70° C. and an endothermic phase change of at least 1 J/g above 125° C.; anda PXRD diffractogram of FIG. 64; and amorphous imipramine, CH3(O(CH2)2)x(OCH2CHCH3)yNH2 pamoate wherein Y/X is 9:1 with an approximate MW of 600, pamoate characterized by at least one method selected from the group consisting of:
an endothermic phase change of at least 50 J/g at a temperature above 240° C.; anda PXRD diffractogram of FIG. 68.