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US 8,940,729 B1Granted
Abuse deterrent and anti-dose dumping pharmaceutical salts useful for the treatment of attention deficit/hyperactivity disorder
AssigneePisgah Laboratories, Inc.
InventorsClifford Riley King, Stephen G. D'Ambrosio, David W. Bristol
Life of this patent
Estimating the term…
Abstract
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.
Claims27
A method for mitigating dose dumping comprising:
- administering a drug product comprising a drug substance consisting essentially of A-B-C wherein A is d-methylphenidate;
- C is an amine other than methylphenidate and B is a bidentate linking group defined by the formula:
- wherein Y1 and Y2 are independently selected from oxygen;
- R10 and R11 are absent;
- G1 and G2 independently represent ionically bound groups A and C;
- R12 and R13 are independently selected from hydrogen, alkyl or 1-6 carbons, alkylacyl of 1-8 carbons or arylacyl of 7-15 carbons;
- R14 will replace one of R15, R16, R17 or R18 and one of R19, R20, R21 or R22 and is an alkyl or branched alkyl of 1-10 carbons, aryl, arylalkyl of 7-15 carbons and wherein R14 may include at least one optically active carbon;
- and
- R15, R16, R17, R18, R19, R20, R21 and R22, are independently selected from hydrogen, alkyl of 1-6 carbons, and wherein adjacent groups may be taken together to form a cyclic alkyl or cyclic aryl moiety;
- and
- wherein said drug substance meets at least one condition in 0.1 N HCl selected from the group consisting of:
- a dissolution rate for said drug substance of no more than 35% of said drug substance is dissolved at 30 minutes with 5 wt % ethanol in said 0.1 N HCl;
- a dissolution rate for said drug substance wherein the percentage of said drug substance dissolved with at least 5 wt % ethanol in said 0.1 N HCl is no more than a percentage of said drug substance dissolved in said 0.1 N HCl without ethanol;
- and
- a dissolution rate for said drug substance wherein the percentage of drug substance dissolved with 40 wt % ethanol in 0.1 N HCl does not exceed 60% while the percentage of drug substance dissolved under the conditions selected from water, 0.1 N HCl, 5 wt % ethanol in 0.1 N HCl and 20 wt % ethanol in 0.1 N HCl does not exceed the drug substance dissolved with 40 wt % ethanol in 0.1 N HCl.
12 more elements
A method for mitigating dose dumping comprising:
- administering a drug product comprising a drug substance wherein said drug substance meets at least one condition in 0.1 N HCl selected from the group consisting of:
- a dissolution rate for said drug substance of no more than 35% of said drug substance is dissolved at 30 minutes with 5 wt % ethanol in said 0.1 N HCl;
- a dissolution rate for said drug substance wherein the percentage of said drug substance dissolved with at least 5 wt % ethanol in said 0.1 N HCl is no more than a percentage of said drug substance dissolved in said 0.1 N HCl without ethanol;
- and
- a dissolution rate for said drug substance wherein the percentage of drug substance dissolved with 40 wt % ethanol in 0.1 N HCl does not exceed 60% while the percentage of drug substance dissolved under the conditions selected from water, 0.1 N HCl, 5 wt % ethanol in 0.1 N HCl and 20 wt % ethanol in 0.1 N HCl does not exceed the drug substance dissolved with 40 wt % ethanol in 0.1 N HCl;
- wherein said drug substance is amorphous d-methylphenidate mono-triethylammonium pamoate with an endothermic phase change of at least 12 J/g at a temperature above 240° C.
3 more elements
A method for mitigating dose dumping comprising:
- administering a drug product comprising a drug substance wherein said drug substance meets at least one condition in 0.1 N HCl selected from the group consisting of:
- a dissolution rate for said drug substance of no more than 35% of said drug substance is dissolved at 30 minutes with 5 wt % ethanol in said 0.1 N HCl;
- a dissolution rate for said drug substance wherein the percentage of said drug substance dissolved with at least 5 wt % ethanol in said 0.1 N HCl is no more than a percentage of said drug substance dissolved in said 0.1 N HCl without ethanol;
- and
- a dissolution rate for said drug substance wherein the percentage of drug substance dissolved with 40 wt % ethanol in 0.1 N HCl does not exceed 60% while the percentage of drug substance dissolved under the conditions selected from water, 0.1 N HCl, 5 wt % ethanol in 0.1 N HCl and 20 wt % ethanol in 0.1 N HCl does not exceed the drug substance dissolved with 40 wt % ethanol in 0.1 N HCl;
- wherein said drug substance is amorphous d-methylphenidate mono-triethylammonium pamoate with an FTIR spectrum of FIG. 51.
3 more elements
A method for mitigating dose dumping comprising:
- administering a drug product comprising a drug substance wherein said drug substance meets at least one condition in 0.1 N HCl selected from the group consisting of:
- a dissolution rate for said drug substance of no more than 35% of said drug substance is dissolved at 30 minutes with 5 wt % ethanol in said 0.1 N HCl;
- a dissolution rate for said drug substance wherein the percentage of said drug substance dissolved with at least 5 wt % ethanol in said 0.1 N HCl is no more than a percentage of said drug substance dissolved in said 0.1 N HCl without ethanol;
- and
- a dissolution rate for said drug substance wherein the percentage of drug substance dissolved with 40 wt % ethanol in 0.1 N HCl does not exceed 60% while the percentage of drug substance dissolved under the conditions selected from water, 0.1 N HCl, 5 wt % ethanol in 0.1 N HCl and 20 wt % ethanol in 0.1 N HCl does not exceed the drug substance dissolved with 40 wt % ethanol in 0.1 N HCl;
- wherein said drug substance is amorphous d-methylphenidate mono-triethylammonium pamoate with a PXRD diffractogram of FIG. 52.
3 more elements
A method for mitigating dose dumping comprising:
- administering a drug product comprising a drug substance wherein said drug substance meets at least one condition in 0.1 N HCl selected from the group consisting of:
- a dissolution rate for said drug substance of no more than 35% of said drug substance is dissolved at 30 minutes with 5 wt % ethanol in said 0.1 N HCl;
- a dissolution rate for said drug substance wherein the percentage of said drug substance dissolved with at least 5 wt % ethanol in said 0.1 N HCl is no more than a percentage of said drug substance dissolved in said 0.1 N HCl without ethanol;
- and
- a dissolution rate for said drug substance wherein the percentage of drug substance dissolved with 40 wt % ethanol in 0.1 N HCl does not exceed 60% while the percentage of drug substance dissolved under the conditions selected from water, 0.1 N HCl, 5 wt % ethanol in 0.1 N HCl and 20 wt % ethanol in 0.1 N HCl does not exceed the drug substance dissolved with 40 wt % ethanol in 0.1 N HCl;
- wherein said drug substance is amorphous d-methylphenidate mono-triethylammonium pamoate with an 1H NMR spectrum of FIG. 53.
3 more elements
A method for mitigating dose dumping comprising:
- administering a drug product comprising a drug substance selected from the group consisting of:
- amorphous d-methylphenidate mono-triethylammonium pamoate characterized by at least one method selected from:
- an endothermic phase change of at least 12 J/g at a temperature above 240° C.;
- and
- a PXRD diffractogram of FIG. 52;
- polymorphic racemic-methylphenidate stearylamine pamoate characterized by at least one method selected from:
- 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. and
- a PXRD diffractogram of FIG. 48;
- amorphous imipramine mono-triethylammonium pamoate characterized by at least one method selected from:
- a DSC thermogram of FIG. 58;
- and
- a PXRD diffractogram of FIG. 60;
- polymorphic imipramine stearylamine pamoate characterized by at least one method selected from:
- a DSC thermogram of FIG. 62;
- and
- a PXRD diffractogram of FIG. 64;
- amorphous imipramine Jeffamine® XTJ-505 pamoate characterized by at least one method selected from:
- a DSC thermogram of FIG. 66;
- and
- a PXRD diffractogram of FIG. 68;
- amorphous hydrocodone stearylamine pamoate characterized by at least one method selected from:
- a DSC thermogram of FIG. 70;
- and
- a PXRD diffractogram of FIG. 72;
- amorphous hydrocodone Jeffamine® XTJ-505 pamoate characterized by at least one method selected from:
- a DSC thermogram of FIG. 74;
- and
- a PXRD diffractogram of FIG. 76;
- wherein said drug substance meets at least one condition in 0.1 N HCl selected from the group consisting of:
- no more than 35% of said drug substance is released at 30 minutes with 5 wt % ethanol in said 0.1 N HCl;
- the percentage of said drug substance released with at least 5 wt % ethanol in said 0.1 N HCl is no more than a percentage of said drug substance released in said 0.1 N HCl without ethanol;
- and
- the percentage of drug substance released with 40 wt % ethanol in 0.1 N HCl does not exceed 60% while the percentage of drug substance released under the conditions selected from water, 0.1 N HCl, 5 wt % ethanol in 0.1 N HCl and 20 wt % ethanol in 0.1 N HCl does not exceed the drug substance released with 40 wt % ethanol in 0.1 N HCl.
33 more elements
Dependencies are inferred from the claim text.