Extended release liquid compositions of guanfacine

Patent metadata

Field	Value
Publication number	US-2016346233-A1
Application number	US-201615148131-A
Country	US
Kind code	A1
Filing date	May 6, 2016
Priority date	May 1, 2014
Publication date	Dec 1, 2016
Grant date	—

Abstract

The present invention relates to extended release liquid compositions of guanfacine. The extended release liquid compositions of the present invention are bioequivalent to marketed extended release tablet compositions of guanfacine. Said extended release liquid compositions provide substantially similar in-vitro dissolution release profile upon storage for at least seven days. Further, the extended release liquid compositions are stable. The extended release liquid compositions are in the form of ready-to-use liquid compositions or reconstituted liquid compositions. It also relates to processes for the preparation of said extended release liquid compositions.

First claim

1 . An extended release liquid composition comprising guanfacine in a pharmaceutically acceptable carrier.

2 . The extended release liquid composition of claim 1 , wherein the composition comprises guanfacine in a concentration from about 0.1 mg/mL to about 12.0 mg/mL of the composition.

3 . The extended release liquid composition of claim 2 , wherein the composition comprises guanfacine in a concentration from about 1.0 mg/mL to about 7.0 mg/mL of the composition.

4 . An extended release liquid composition comprising guanfacine in a pharmaceutically acceptable carrier, wherein the extended release liquid composition is bioequivalent to the marketed extended release tablet composition of guanfacine.

5 . The extended release liquid composition of claim 4 , wherein the composition exhibits an area under the curve (AUC) 0→∞ ranging from about 34000 hr*pg/mL to about 220000 hr*pg/mL upon administration of a 4 mg dose of guanfacine under fasting state.

6 . (canceled)

7 . The extended release liquid composition of claim 4 , wherein the composition exhibits an area under the curve (AUC) last ranging from about 32000 hr*pg/mL to about 180000 hr*pg/mL upon administration of a 4 mg dose of guanfacine under fasting state.

8 . (canceled)

9 . The extended release liquid composition of claim 4 , wherein the composition exhibits C max from about 1800 pg/mL to about 9000 pg/mL upon administration of a 4 mg dose of guanfacine under fasting state.

10 . (canceled)

11 . The extended release liquid composition of claim 4 , wherein the composition exhibits T max from about 2 hours to about 10 hours, upon administration of a 4 mg dose of guanfacine under fasting state.

12 . The extended release liquid composition of claim 4 , wherein the composition exhibits T lag of less than about 2 hours, upon administration of a 4 mg dose of guanfacine under fasting state.

13 . The extended release liquid composition of claim 1 , wherein the composition is characterized by having an in-vitro dissolution release profile when determined for 4 mg dose of 1 mg/mL concentration composition using USP type II apparatus at 75 rpm, in 900 mL of hydrochloric acid buffer with a pH of 2.2 at 37° C. as follows:
a. not more than about 30% of guanfacine released after 1 hour,
b. about 35% to about 75% of guanfacine released after 4 hours, and;
c. not less than about 75% of guanfacine released after 24 hours.

14 . The extended release liquid composition of claim 13 , wherein the in-vitro dissolution release profile of the extended release liquid composition upon storage for at least seven days remains substantially similar to the initial in-vitro dissolution release profile.

15 . An extended release liquid composition comprising guanfacine in a pharmaceutically acceptable carrier, wherein the composition is a stable composition.

16 . The extended release liquid composition of claim 15 , wherein the composition comprises less than about 1.0% w/w of 2, 6-dichlorophenyl acetic acid.

17 . (canceled)

18 . The extended release liquid composition of claim 15 , wherein the composition comprises less than about 3.0% w/w of total related substances.

19 . (canceled)

20 . [[An]] The extended release liquid composition of claim 1 wherein the composition has a pH of less than about 6.8.

21 . The extended release liquid composition of claim 1 , wherein the composition is a ready-to-use liquid composition or a reconstituted liquid composition.

22 . (canceled)

23 . (canceled)

24 . An extended release liquid composition comprising guanfacine in a pharmaceutically acceptable carrier, wherein the composition comprises:
i. cores comprising guanfacine and a release-controlling agent; and ii. a pharmaceutically acceptable carrier.

25 . The extended release liquid composition of claim 24 , wherein guanfacine may be present in the core or layered over an inert particle to form a core.

26 . (canceled)

27 . The extended release liquid composition of claim 24 , wherein the release-controlling agent is present within the core or coated over the guanfacine core or both.

28 . The extended release liquid composition of claim 24 , wherein the release-controlling agent is selected from the group consisting of a pH-dependent release controlling agent, a pH-independent release controlling agent, and mixtures thereof.

29 . (canceled)

30 . (canceled)

31 . The extended release liquid composition of claim 24 , wherein the core further comprises one or more pharmaceutically acceptable excipients selected from the group consisting of acids, osmogents, binders, glidants, and combinations thereof.

32 . The extended release liquid composition of claim 24 , wherein the carrier comprises one or more of liquid adjuvants and other pharmaceutically acceptable excipients.

33 . The extended release liquid composition of claim 32 , wherein the other pharmaceutically acceptable excipients in the carrier are selected from the group comprising acids, osmogents, buffering agents, suspending agents, glidants, sweetening agents, flavors, colorants, anti-caking agents, wetting agents, preservatives, antioxidants, chelating agents, binders, viscosity modifiers, and combinations thereof.

34 . The extended release liquid composition of claim 24 , wherein cores comprising guanfacine and a release-controlling agent have a particle size d 90 value of less than about 1.5 mm.

35 . The extended release liquid composition of claim 24 , wherein the composition is characterized by having an osmolality ratio of at least about 1.

36 . The extended release liquid composition of claim 24 , wherein the pharmaceutically acceptable carrier has an osmolality of about 1 osmol/kg or more than about 1 osmol/kg of the pharmaceutically acceptable carrier.

37 . The extended release liquid composition of claim 24 , wherein the composition further comprises guanfacine in an immediate release form.

38 . A method of treating Attention Deficit Hyperactivity Disorder by administering the extended release liquid composition of claim 1 .

39 . The method of treating Attention Deficit Hyperactivity Disorder, wherein the extended release liquid composition of claim 1 is administered once daily.

Assignees

• Sun Pharmaceutical Ind Ltd

Inventors

• Singh Romi Barat
• Ramaraju Kalaiselvan
• Mondal Balaram
• Kumar Ashish
• Kaushik Suchitra

Classifications

• A61K31/165 Primary

  having aromatic rings, e.g. colchicine, atenolol, progabide · CPC title

• A61K9/145

  with organic compounds · CPC title

• A61K9/5078

  with drug-free core · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• A61K9/5042

  Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose · CPC title