Claims for Patent: 11,918,689

Summary for Patent: 11,918,689

Title:	Liquid clonidine extended release composition
Abstract:	An oral clonidine dosage unit providing a twenty-four hour extended release profile following a single dose administration is provided. The dosage unit comprises a pharmaceutically effective amount of a coated complex comprising clonidine bound to a cationic exchange resin, which is characterized by a twenty-four hour release profile. Dosage units may also provide an immediate release component.
Inventor(s):	Grishma Patel
Assignee:	PROVIDENT BANK
Application Number:	US17/387,517
Patent Claims:	1. An extended release oral clonidine aqueous suspension which provides a once-a-day therapeutic effect for clonidine 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 particle and is in a layer over the clonidine-cation exchange resin complex-matrix particles; wherein the modified release 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 in the matrix comprises about 5% w/w to about 20% w/w of the particles: wherein the modified release barrier coated clonidine-cation exchange resin complex-matrix particles provide about 70% w/w to about 95% w/w of the total clonidine in the suspension, 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, wherein the immediate release clonidine component(s) provide about 5% w/w to about 30% w/w of the total clonidine in the suspension, as determined based on the amount of clonidine equivalent to clonidine HCl; and an aqueous suspension base. 2. The extended release oral clonidine aqueous suspension according to claim 1 which further comprises about 0.1% w/v to about 0.5% w/v of an anti-oxidant, and a buffering component. 3. The extended release oral clonidine aqueous suspension according to 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. 4. The extended release oral clonidine aqueous suspension according to claim 1, wherein the immediate release clonidine components comprise the immediate release clonidine-cation exchange resin complex and a pharmaceutically acceptable salt of clonidine uncomplexed to an ion exchange resin. 5. The extended release-oral clonidine aqueous suspension according to claim 1, wherein the ratio of clonidine to cation exchange resin in the complex of (A) and/or (B) is about 1 parts clonidine by weight to about 300 parts resin by weight. 6. The extended-release oral clonidine aqueous suspension according to claim 5, wherein the ratio of clonidine to cation exchange resin in the complex of (A) and/or (B) is about 1 parts clonidine by weight to about 150 parts resin by weight. 7. The extended release oral clonidine aqueous suspension according to claim 5, wherein the ratio of clonidine to cation exchange resin in the complex of (A) and/or (B) is about 1 parts clonidine by weight to about 25 parts resin by weight. 8. The extended release oral clonidine aqueous suspension according to claim 1, wherein the barrier coating is: at least one pH-independent barrier coating of (a) ethylcellulose and at least one plasticizer; (b) a cured polyvinyl acetate and at least one plasticizer, (c) a pH-independent acrylate based coating and an optional plasticizer, or (d) mixtures of any of (a), (b), and/or (c). 9. The extended release oral clonidine aqueous suspension according to claim 8, wherein the 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. 10. The extended release oral clonidine aqueous suspension according to claim 1, wherein the barrier coating comprises 49.5% w/w to 60.5% w/w of the coated particles. 11. The extended release oral clonidine aqueous suspension according to claim 1, wherein the hydrophilic polymer or co-polymer in the matrix comprises a polyvinylpyrrolidone. 12. The extended release oral clonidine aqueous suspension according to claim 1, wherein the hydrophilic polymer or co-polymer in the matrix is about 5% w/w to about 10% w/w of the barrier clonidine-cation exchange resin complex-matrix. 13. The extended hour release oral clonidine aqueous suspension according to claim 1, wherein the cation exchange resin of (A) and/or (B) comprises a sulfonated copolymer of styrene and divinylbenzene and a mobile (exchangeable) cation is sodium with a total cation exchange capacity of about 5 meq/g, and further comprises 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 has about 9.4% to 11.5% sodium, a potassium exchange capacity of 110 to 135 mg/g, a heavy metals content of less than 10 ppm. 14. The extended release oral clonidine aqueous suspension according to claim 1, wherein the suspension provides a single plasma concentration peak for clonidine post-dosing under fasting conditions. 15. The extended release oral clonidine aqueous suspension according to claim 1, wherein the suspension provides one or more of the pharmacokinetic parameters for clonidine of: (a) an arithmetic mean Cmax (pg/mL) of about 326 pg/mL to about 508 pg/mL; and/or (b) an arithmetic mean AUC0-∞ (hr-pg/mL) of about 10,650 hr-pg/mL to about 16,650 hr-pg/mL; and/or (c) an arithmetic mean Tmax (hr) of about 14 hours to 22 hours; as assessed following dosing two times in a day separated by about 12 hours interval, 0.1 mg clonidine at each dosing time (i.e., at 0 and 12 hours) to provide a total daily dose of 0.2 mg clonidine, based on the equivalent to clonidine HCl. 16. The extended release oral clonidine aqueous suspension according to claim 15, wherein the suspension provides one or more of the pharmacokinetic parameters for clonidine of: (a) an arithmetic mean Cmax (pg/mL) of about 350 pg/mL to about 450 pg/mL; and/or (b) an arithmetic mean AUC0-∞ (hr-pg/mL) of about 12,500 hr-pg/mL to about 14,550 hr-pg/mL; and/or (c) an arithmetic mean Tmax (hr) of about 15.5 hours to about 20.5 hour. 17. A method for delivering an effective amount of clonidine fora twenty-four hour period comprising administering to a subject a single oral clonidine composition according to claim 1 prior to bed time. 18. The extended release oral clonidine aqueous suspension according to claim 1, wherein the suspension is at pH of about 3 to about 3.5. 19. The extended release oral clonidine aqueous suspension according to claim 1, wherein the immediate release clonidine component(s) provide about 10% w/w of the total clonidine in the suspension, as determined based on the amount of clonidine equivalent to clonidine HCl.