Granted Patent
B2
US 12,201,610 · App. 18/618,520 · Granted Jan 21, 2025
Compositions comprising aticaprant
Inventors:
Nicolaas Martha Felix Goyvaerts (Beerse, BE); Mark Schmidt (Antwerp, BE); Vanina Popova (Nijlen, BE); Adam Savitz (Greenwich, CT); Rama Melkote (Basking Ridge, NJ); Wayne C. Drevets (Rancho Santa Fe, CA); Srihari Gopal (Belle Mead, NJ); Darrel Pemberton (Oud Turnhout, BE); Chakradhar Lagishetty (King of Prussia, PA); Iva Kezic (Antwerp, BE); Mahesh N. Samtani (Flemington, NJ); Tom Huybrechts (Merelbeke, BE); Geert Van der Avoort (Retie, BE); Matthieu Ravelingien (Geel, BE); Laura Martinez Marcos (Antwerp, BE); Tatiana Marcozzi (Antwerp, BE); Katarina Jokicevic (Mortsel, BE)
Assignee:
Janssen Pharmaceuticals, Inc.
A61K31/40A61K9/2009A61K9/2013A61K9/2018A61K9/2054A61K9/2853A61K9/4825A61K9/4858A61K9/4866A61K45/06A61P25/24
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Abstract
The present disclosure relates to compositions, including oral compositions in the form of tablets, comprising aticaprant and methods of using the same.
Claims (32)
1. A pharmaceutical composition in the form an oral tablet comprising about 5 mg to about 10 mg of aticaprant, wherein the oral tablet comprises a core tablet having an intragranular and extragranular phase, wherein:
the intragranular phase comprises the aticaprant, a filler, a disintegrant, and a glidant;
the extragranular phase comprises a filler, a disintegrant, and a lubricant; and
the ratio of intragranular to extragranular phase is between about 1.5 and about 3 by weight.
2. The pharmaceutical composition of claim 1 , wherein the intragranular phase comprises one or more of: an aticaprant to filler ratio of about 0.01 and about 1 by weight; an aticaprant to disintegrant ratio of about 0.5 to about 8 by weight; and an aticaprant to glidant ratio of about 1 to about 10 by weight.
3. The pharmaceutical composition of claim 2 , wherein the extragranular phase comprises one or more of: a filler to disintegrant ratio of about 20 to about 80 by weight; and a filler to lubricant ratio of about 5 to about 100 by weight.
4. The pharmaceutical composition of claim 3 , wherein the filler in the intragranular and the extragranular phase is, independently, microcrystalline cellulose, lactose monohydrate, or silicified microcrystalline cellulose, or a combination thereof.
5. The pharmaceutical composition of claim 4 , wherein the disintegrant in the intragranular and the extragranular phase is, independently, croscarmellose sodium.
6. The pharmaceutical composition of claim 5 , wherein the glidant is silica, colloidal anhydrous.
7. The pharmaceutical composition of claim 1 , wherein the intragranular phase comprises about 50 to about 70 mg microcrystalline cellulose, about 50 to about 70 mg lactose monohydrate, about 4 to about 6 mg croscarmellose sodium, and about 1 to about 3 mg silica, colloidal anhydrous; and wherein the extragranular phase comprises about 50 to about 70 mg silicified microcrystalline cellulose, about 4 to about 6 mg croscarmellose sodium, and about 1 to about 3 mg magnesium stearate.
8. The pharmaceutical composition of claim 1 , wherein the intragranular phase comprises about 60 mg microcrystalline cellulose, about 60 mg lactose monohydrate, about 5 mg croscarmellose sodium, and about 2 mg silica, colloidal anhydrous; and wherein the extragranular phase comprises about 57 mg silicified microcrystalline cellulose, about 5 mg croscarmellose sodium, and about 2 mg magnesium stearate.
9. The pharmaceutical composition of claim 1 , wherein the composition has a pharmacokinetic (PK) profile comprising one or more of the following parameters after administration of the composition to a human after at least a 10-hour fast (dose-normalized to 10 mg):
a. a mean C max between about 30 and 40 ng/ml;
b. a mean AUC infinity between about 300 and 430 h*ng/ml;
c. a mean AUC last between about 280 and 430 h*ng/ml;
d. a median t max between about 1 to 4 hours.
10. The pharmaceutical composition of claim 9 , wherein the mean C max is between about 30 and 35 ng/mL.
11. The pharmaceutical composition of claim 9 , wherein the mean AUC infinity is between about 300 and 320 h*ng/mL.
12. The pharmaceutical composition of claim 9 , wherein the mean AUC last is between about 280 and 310 h*ng/mL.
13. The pharmaceutical composition of claim 9 , wherein the median t max is about 1.5 hours.
14. The pharmaceutical composition of claim 1 , wherein the composition has a dissolution profile comprising a Q value of between about 60% and 90% at 45 minutes, under the following dissolution operating conditions:
Apparatus: Paddle (USP Type 2, Ph. Eur., JP)
Dissolution medium: 0.01 M hydrochloric acid
Volume: 900 mL
Temperature: 37+/−0.5 degrees Celsius
Rotation Speed: 50 rpm
Analytical Finish: UHPLC with UV detection at 247 nm.
15. The pharmaceutical composition of claim 14 , wherein the Q value is between about 70% and 80% at 45 minutes.
16. The pharmaceutical composition of claim 14 , wherein the Q value is about 75% at 45 minutes.
17. The pharmaceutical composition of claim 1 , wherein the oral tablet comprises a film coat.
18. The pharmaceutical composition of claim 17 , wherein the ratio of the film coat to core tablet is between about 0.03 to about 10 by weight.
19. The pharmaceutical composition of claim 18 , wherein the film coat comprises a coating powder.
Continuity (3)
Provisional Application
63317471
· Mar 7, 2022
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