ORAL COMPOSITION OF CELECOXIB FOR TREATMENT OF PAIN
The present invention relates to a stable oral liquid pharmaceutical composition of celecoxib or its pharmaceutically acceptable salts thereof. The celecoxib present in the compositions as described herein do not show any precipitation when subjected in Fasted-State Simulated Gastric Fluid (FaSSGF) at pH 2.0, temperature of 37° C.±0.5° C. and under stirring at a speed of 50 rpm at least for 60 minutes. It also relates to the process of preparing and method of using said composition of celecoxib.
1 . A pharmaceutical composition comprising a therapeutically effective amount of celecoxib, wherein said composition has a mean droplet size of not more than 500 nm, when tested in 250 ml of Fasted-State Simulated Gastric Fluid (FaSSGF) at pH of 2.0, temperature of 37° C.±0.5° C. and under stirring at a speed of 50 rpm.
2 . The composition of claim 1 , wherein said therapeutically effective amount of celecoxib comprises a reduced dose of celecoxib relative to conventional celecoxib 400 mg capsules.
3 . The composition of claim 2 , wherein said reduced dose of celecoxib is at least about 20% less than conventional celecoxib in 400 mg oral capsules.
4 . The composition of claim 2 , wherein said reduced dose of celecoxib is at least about 40% less than conventional celecoxib in 400 mg oral capsules.
5 . The composition of claim 2 , wherein said reduced dose of celecoxib is at least about 55% less than conventional celecoxib in 400 mg oral capsules.
6 . The composition of claim 2 , wherein said reduced dose of celecoxib is at least about 70% less than conventional celecoxib in 400 mg oral capsules.
7 . The composition of claim 2 , wherein said reduced dose of celecoxib is about 320 mg.
8 . The composition of claim 2 , wherein said reduced dose of celecoxib is about 240 mg.
9 . The composition of claim 2 , wherein said reduced dose of celecoxib is about 180 mg.
10 . The composition of claim 2 , wherein said reduced dose of celecoxib is about 120 mg.
11 . The composition of claim 1 , wherein said composition comprises at least one solubilizer.
12 . The composition of claim 1 , wherein said composition comprises at least one medium chain glyceride.
13 . The composition of claim 1 , wherein said composition comprises at least one polar solvent.
14 . The composition of claim 1 , wherein said composition upon oral administration to a human subject under fasting conditions, provides at least one of the following pharmacokinetic parameters:
a) AUC (0-15 min) from about 10 ng·h/mL to about 80 ng·h/mL;
b) AUC (0-30 min) from about 80 ng·h/mL to about 400 ng·h/mL;
c) AUC (0-1 hr) from about 400 ng·h/mL to about 1500 ng·h/mL;
d) AUC (0-2 hr) from about 1000 ng·h/mL to about 4000 ng·h/mL;
e) AUC (0-t) of at least about 2000 ng·h/mL;
f) AUC (0-∞) of at least about 2000 ng·h/mL.
15 . The composition of claim 1 , wherein said composition upon oral administration to a human subject under fasting conditions provides higher AUC 0-15 min , AUC 0-30 min , AUC 0-1 hour , and AUC 0-2 hour compared to conventional celecoxib 400 mg capsules.
16 . The composition of claim 2 , wherein said composition upon oral administration to a human subject under fasting conditions, provides at least 50 times higher AUC (0-15 min) as compared to conventional celecoxib 400 mg oral capsules.
17 . The composition of claim 2 , wherein said composition upon oral administration to a human subject under fasting conditions, provides at least one of the following pharmacokinetic parameters:
a) AUC (0-15 min) from about 10 ng·h/mL to about 80 ng·h/mL;
b) AUC (0-30 min) from about 80 ng·h/mL to about 400 ng·h/mL;
c) AUC (0-1 hr) from about 400 ng·h/mL to about 1500 ng·h/mL;
d) AUC (0-2 hr) from about 1000 ng·h/mL to about 4000 ng·h/mL;
e) AUC (0-t) of at least about 2000 ng·h/mL;
f) AUC (0-∞) of at least about 2000 ng·h/mL; and
g. T lag of not more than 10 minutes.
18 . The composition of claim 1 , wherein said composition upon oral administration to a human subject under fasting conditions, provides T lag of not more than 10 minutes.
19 . The composition of claim 1 , wherein said composition does not show any precipitation for at least 4 hours.
20 . The composition of claim 1 , wherein said composition does not show any precipitation for at least 3 hours.
21 . The composition of claim 1 , wherein said composition does not show any precipitation for at least 2 hours.
22 . The composition of claim 1 , wherein said composition does not show any precipitation for at least 60 minutes.
23 . A method of treating pain, the method comprising administering the composition of claim 1 to a subject in need thereof.
24 . The method of claim 23 , wherein the composition is administered orally.
25 . The method of claim 24 , wherein administration of the composition provides at least one of the pharmacokinetic parameters of claim 14 .
26 . The method of claim 23 , wherein said pain is acute pain, migraine pain, cluster headache, neuropathic pain, post-operative pain, chronic lower back pain, herpes neuralgia pain, phantom limb pain, central pain, dental pain, neuropathic pain, opioid-resistant pain, visceral pain, surgical pain, bone injury pain, pain during labor and delivery, pain resulting from burns, sunburn pain, post-partum pain, angina pain, genitourinary tract-related pain, cystitis pain, arthritis pain, inflammation pain, osteoarthritis pain, juvenile rheumatoid arthritis pain, ankylosing spondylitis pain, or primary dysmenorrhea pain.
27 . The method of claim 23 , wherein said pain is migraine pain.
28 . The method of claim 23 , wherein said pain is acute pain.