Formulations of enzalutamide

Patent metadata

Field	Value
Publication number	US-2023122911-A1
Application number	US-202217985220-A
Country	US
Kind code	A1
Filing date	Nov 11, 2022
Priority date	Sep 11, 2012
Publication date	Apr 20, 2023
Grant date	—

Abstract

This disclosure provides formulations of enzalutamide and their use for treating hyperproliferative disorders.

First claim

1 . A method of treating prostate cancer comprising:
orally administering to a male human in need thereof two tablets, wherein each of the two tablets comprises:
(a) a spray-dried dispersion consisting essentially of 80 mg amorphous enzalutamide and 400 mg hydroxypropyl methylcellulose acetate succinate; and
(b) one or more inactive excipients.

2 . The method according to claim 1 , wherein the two tablets, when orally dosed to a cohort of male humans each receiving a single 160 mg dose of enzalutamide, result in an area under the concentration-time curve from the time of dosing to seven days after dosing that is greater than 150 µg·hr/ml.

3 . The method according to claim 1 , wherein the two tablets, when orally dosed to a cohort of male humans each receiving a 160 mg dose of enzalutamide, results in an area under the concentration-time curve that is equivalent to the area under the concentration-time curve that results from orally dosing four capsules to a cohort of male humans, wherein each of the four capsules comprises 40 mg enzalutamide dissolved in 904.96 mg caprylocaproyl polyoxylglycerides.

4 . The method according to claim 3 , wherein the area under the concentration-time curve is from the time of dosing to the last measurable concentration.

5 . The method according to claim 3 , wherein the area under the concentration-time curve is from the time of dosing to infinity.

6 . The method according to claim 1 , wherein the amorphous enzalutamide remains amorphous following storage of the spray-dried dispersion at 40° C. and 75% relative humidity for one month.

7 . The method according to claim 1 , wherein the spray-dried dispersion has a glass transition temperature greater than 50° C. following equilibration overnight at ambient temperature and 75% relative humidity.

8 . The method according to claim 1 , wherein each of the two tablets, when evaluated individually by a liquid-replacement dissolution test in which a paddle method (50 rpm) is started using 300 mL of 0.03 N hydrochloric acid (pH 1.2) and the liquid conditions for the dissolution test are changed to pH 6.8 and 900 mL after 30 minutes, provides an enzalutamide concentration of at least about 60 µg/mL at a time that is not more than 90 minutes.

9 . The method according to claim 8 , wherein, when each of the two tablets is evaluated individually by the liquid-displacement dissolution test, provides an enzalutamide concentration of at least about 60 µg/mL at a time that is not more than 60 minutes.

10 . The method according to claim 1 , wherein the one or more inactive excipients comprise croscarmellose sodium and magnesium stearate.

11 . The method according to claim 10 , wherein the one or more inactive excipients further comprise microcrystalline cellulose and colloidal silicon dioxide.

12 . The method according to claim 1 , wherein the spray-dried dispersion is approximately 70% of the total tablet weight for each of the two tablets.

13 . The method according to claim 10 , wherein the croscarmellose sodium is 6% to 10% of the total tablet weight for each of the two tablets.

14 . The method according to claim 1 , wherein each of the two tablets is film-coated.

Assignees

• Astellas Pharma Inc
• Medivation Prostate Therapeutics Llc

Inventors

• Lorenz Douglas Alan
• Konagurthu Sanjay
• Wald Randy J
• Everett Jason A
• Matz Sheila
• Takaishi Yuuki
• Sakai Toshiro
• Irie Ryousuke
• Oba Shinsuke
• Toyota Hiroyasu
• Nishimura Koji
• Kanbayashi Atsushi

Classifications

• A61K31/4166

  having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin · CPC title

• C07D233/86

  Oxygen and sulfur atoms, e.g. thiohydantoin · CPC title

• A61K31/4164 Primary

  1,3-Diazoles · CPC title

• A61K9/2054 Primary

  Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose · CPC title

• A61K9/2027

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title