Granted Patent B2

US 12,576,032 · App. 18/419,883 · Granted Mar 17, 2026

Inventor: Grishma Patel (East Brunswick, NJ)

Assignee: Tris Pharma, Inc.

A61K9/1635A61K9/0053A61K9/08A61K9/1647A61K9/1652A61K31/4168A61K45/06A61K47/183A61K47/22

Abstract

Claims (44)

1 . A method for treating attention deficit hyperactivity disorder comprising administering to a subject a single dosage of an extended release oral clonidine aqueous suspension comprising:

(A) a pharmaceutically effective amount of modified release barrier coated clonidine—cation exchange resin complex—matrix particles, wherein the particles each comprise clonidine bound to a cationic exchange resin in a matrix comprising a hydrophilic polymer or co-polymer, wherein the modified release barrier coating comprises 50% w/w to about 80% w/w of the clonidine—cation exchange resin complex—matrix particle based on particle weight prior to barrier coating and is in a layer over the clonidine—cation exchange resin complex—matrix particles; wherein the barrier coating comprises a pH-independent, water-insoluble polymer and a plasticizer and provides modified release to the clonidine in the barrier coated particles wherein the hydrophilic polymer or co-polymer in the matrix comprises about 5% w/w to about 20% w/w of the clonidine—cation exchange resin complex—matrix particles based on weight prior to the barrier coating;

wherein at least about 70% w/w to about 95% w/w of the clonidine in the suspension is provided by the modified release barrier coated clonidine—cation exchange resin complex—matrix particles, as determined based on the amount of clonidine equivalent to clonidine HCl;

(B) an immediate release clonidine component(s) comprising (1) an immediate release clonidine—cation exchange resin complex or (2) (a) an immediate release clonidine—cation exchange resin complex and (b) clonidine uncomplexed to an ion exchange resin, a pharmaceutically acceptable salt of clonidine uncomplexed to an ion exchange resin, or a combination thereof; and

an aqueous suspension base.

2 . The method of claim 1 , wherein the dose of the suspension comprises 0.1 mg clonidine per mL or 0.2 mg clonidine per mL suspension, as determined based on the equivalent to clonidine HCl.

3 . The method of claim 1 , wherein the suspension comprises 5% w/w to about 30% w/w clonidine in immediate release form, as determined based on the amount of clonidine equivalent to clonidine HCl.

4 . The method of claim 3 , wherein the suspension provides a single plasma concentration peak for clonidine post-dosing under fasting conditions.

5 . The method of claim 1 , wherein the suspension further comprises about 0.1% w/v to about 0.5% w/v of an anti-oxidant.

6 . The method of claim 2 , wherein the anti-oxidant comprises an ethylene-diamine-tetra-acetic acid or a pharmaceutically acceptable water soluble salt thereof, ethyl maltol, or mixtures thereof.

7 . The method of claim 1 , wherein the immediate release clonidine component comprises an immediate release clonidine—cation exchange resin complex.

8 . The method of claim 1 , wherein the suspension further comprises a clonidine or pharmaceutically acceptable salt.

9 . The method of claim 1 , wherein the suspension comprises un-complexed cation exchange resin.

10 . The method of claim 1 , wherein the modified release barrier coating is selected from: at least one pH-independent barrier coating polymer selected from (a) ethylcellulose and at least one plasticizer; (b) a cured polyvinyl acetate and at least one plasticizer, or (c) a pH-independent acrylate based coating and an optional plasticizer, or (d) mixtures of any of (a), (b), and/or (c).

11 . The method of claim 1 , wherein the modified release barrier coating comprises about 70% w/w to about 90% w/w polyvinyl acetate and about 2.5% w/w to about 20% w/w plasticizer.

12 . The method of claim 1 , wherein the hydrophilic polymer or co-polymer in the matrix comprises a polyvinylpyrrolidone.

13 . The method of claim 1 , wherein the cation exchange resin comprises a sulfonated copolymer of styrene and divinylbenzene and an average particle size of 10% to 25% in the range of 0.075 mm and no more than 1% being greater than 0.150 mm in size and a heavy metals content of less than 10 ppm.

14 . The method of claim 1 , wherein the suspension further comprises 5% w/w to about 30% w/w clonidine in immediate release form.

15 . The method of claim 14 , wherein the suspension provides a single plasma concentration peak for clonidine post-dosing under fasting conditions.

16 . The method of claim 1 , wherein the suspension comprises an effective amount of clonidine for a twenty-four hour period.

17 . The method of claim 1 , wherein the method comprises administering to a subject the suspension prior to bed time.

18 . The method of claim 16 , wherein the administering of the suspension is with food or without food.

19 . The method of claim 16 , wherein the dose of the suspension comprises 0.1 mg clonidine per mL or 0.2 mg clonidine per mL, as determined based on the equivalent to clonidine HCl.

20 . The method of claim 16 , wherein the dose of the suspension comprises up to 0.4 mg clonidine per mL suspension, as determined based on equivalent to clonidine HC 1 .

21 . The method of claim 1 , in which the modified release barrier coated clonidine—cation exchange resin complex—matrix particles provide about 90% w/w of the total clonidine in the suspension, and about 10% w/w clonidine in immediate release form.

22 . The method of claim 1 , wherein the subject is a pediatric patient.

23 . The method of claim 1 , wherein the subject is aged 6 to 17.

24 . The method of claim 1 , wherein the suspension further comprises a buffering component.

25 . A method for treating attention deficit hyperactivity disorder once a day comprising administering to a subject a single dose of an extended release oral clonidine aqueous suspension comprising:

(A) a pharmaceutically effective amount of modified release barrier coated clonidine—cation exchange resin complex—matrix particles, wherein the particles each comprise clonidine bound to a cationic exchange resin in a matrix comprising a hydrophilic polymer or co-polymer, wherein the modified release barrier coating comprises 50% w/w to about 80% w/w of the clonidine—cation exchange resin complex—matrix particle based on particle weight prior to the barrier coating and, the modified release coating is in a layer over the clonidine—cation exchange resin complex—matrix particles; wherein the barrier coating comprises a pH-independent, water-insoluble polymer and a plasticizer and provides modified release to the clonidine in the barrier coated particles wherein the hydrophilic polymer or co-polymer in the matrix comprises about 3% w/w to about 20% w/w of the clonidine—cation exchange resin complex—matrix particle based on weight prior to the barrier coating;

wherein about 70% w/w to about 95% w/w clonidine in the suspension is provided by the modified release barrier coated clonidine—cation exchange resin complex—matrix particles, as determined based on the amount of clonidine equivalent to clonidine HCI;

(B) about 5% w/w to about 30% w/w clonidine in the suspension in an immediate release form, the immediate release form comprising an immediate release clonidine—cation exchange resin complex, clonidine uncomplexed to an ion exchange resin, and a pharmaceutically acceptable salt of clonidine uncomplexed to an ion exchange resin, as determined based on the amount of clonidine equivalent to clonidine HCl; and

an aqueous suspension base.

26 . The method of claim 25 , in which the modified release barrier coated clonidine—cation exchange resin complex—matrix particles provide about 90% w/w of clonidine, as determined based on the total clonidine in the suspension.

27 . The method of claim 25 , wherein the suspension comprises about 5% w/w immediate release clonidine-cation exchange resin complex and about 5% w/w clonidine uncomplexed to an ion exchange resin in immediate release form, as determined based on the total clonidine equivalent to clonidine HCl in the suspension.

28 . The method of claim 25 , wherein the suspension further comprises one or more buffering agent, one or more anti-oxidant, one or more preservative, one or more suspending agent, one or more flavoring agent, one or more solvents, or combinations thereof.

29 . The method of claim 25 , wherein the matrix forming polymer comprises polyvinylpyrrolidone.

30 . A method for treating attention deficit hyperactivity disorder once a day comprising administering to a subject a single dose of an extended release oral clonidine aqueous suspension comprising:

(A) a pharmaceutically effective amount of modified release barrier coated clonidine—cation exchange resin complex—matrix particles, wherein the particles each comprise clonidine bound to a cationic exchange resin in a matrix comprising a hydrophilic polymer or co-polymer which comprises about 3% w/w to about 20% w/w of the particles, wherein the modified release barrier coating is about 50% w/w to about 80% w/w of the clonidine—cation exchange resin complex—matrix particle based on particle weight prior to barrier coating and the barrier coating is in a layer over the clonidine—cation exchange resin complex-matrix particles and comprises a pH-independent, water-insoluble polymer and a plasticizer;

wherein about 90% w/w of the clonidine in the suspension is provided by the modified release barrier coated clonidine—cation exchange resin complex—matrix particles, as determined based on the amount of clonidine equivalent to clonidine HCl;

(B) about 10% w/w of the clonidine in the suspension in an immediate release form, the immediate release form comprising an immediate release clonidine-cation exchange resin complex, clonidine uncomplexed to an ion exchange resin, and a pharmaceutically acceptable salt of clonidine uncomplexed to an ion exchange resin, as determined based on the amount of clonidine equivalent to clonidine HCl; and

an aqueous suspension base.

31 . The method of claim 30 , wherein the suspension comprises about 5% w/w immediate release clonidine—cation exchange resin complex and about 5% w/w clonidine uncomplexed to an ion exchange resin in immediate release form, as determined based on the total clonidine equivalent to clonidine HCl in the suspension.

32 . The method of claim 30 , wherein the suspension further comprises one or more buffering agent, one or more anti-oxidant, one or more preservative, one or more suspending agent, one or more flavoring agent, one or more solvents, or combinations thereof.

Assignments (3)

Continuity (3)

References Cited (224)