Extended release tablet formulations of flibanserin and method for manufacturing the same

• US 8,658,207 B2
• Filed: 08/13/2007
• Issued: 02/25/2014
• Est. Priority Date: 08/14/2006
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Eisenreich, Wolfram, Friedl, Thomas, Sommer, Florian, Pearnchob, Nantharat, Wagner, Karl G.
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Palenik, Jeffrey T
• Application Number:
  US11/837,959
• Publication Number:
  US 20080038347A1
• Time in Patent Office: 2,388 Days
• Field of Search: None
• US Class Current: 424/468
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/497 containing further heterocyclic rings
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention provides pharmaceutical release systems comprising an therapeutically effective amount of flibanserin and at least one pharmaceutically acceptable excipient, characterized in that said pharmaceutical release systems exhibit a pharmacokinetic profile that is characterized by an average maximum flibanserin plasma concentration C_max lower than 300 ng/mL, preferably lower than 200 ng/mL after administration of a single dose to healthy volunteers in fasted state or directly after a meal.

Claims

1. A pharmaceutical release system comprising:

(a) a therapeutically effective amount of flibanserin, or pharmaceutically acceptable salt thereof,

(b) a pharmaceutically acceptable pH-dependent polymer;

(c) a pharmaceutically acceptable pH-independent polymer; and

(d) a pharmaceutically acceptable acid,

wherein the composition exhibits a pharmacokinetic profile that is characterized by an average maximum flibanserin plasma concentration C_max of less than 300 ng/mL and an average total systemic exposure between 1300 and 3000 ng·

h/mL after administration of a single daily dose to healthy volunteers in fasted state or directly after a meal.

2. The pharmaceutical release system according to claim 1, characterized by an average maximum flibanserin plasma concentration C_max of less than 300 ng/mL and an average total systemic exposure between 1500 and 2500 ng·

h/mL after administration of a single daily dose to healthy volunteers in fasted state or directly after a meal.

3. The pharmaceutical release system according to claim 1, characterized by having an in vitro dissolution profile such that at least 1% w/w and no more than 60% w/w of the flibanserin is released at 1 hour;

at least 5% w/w and up to 70% w/w of the flibanserin is released at 4 hours;

at least 30% w/w and up to 100% w/w of the flibanserin is released at 12 hours, when dissolution is measured using a USP (Type II) apparatus.

4. The pharmaceutical release system according to claim 2, characterized by having an in vitro dissolution profile such that at least 1% w/w and no more than 60% w/w of the flibanserin is released at 1 hour;

at least 5% w/w and up to 70% w/w of the flibanserin is released at 4 hours;

at least 30% w/w and up to 100% w/w of the flibanserin is released at 12 hours, when dissolution is measured using a USP (Type II) apparatus.

5. The pharmaceutical release system according to claim 1, characterized by having an in vitro dissolution profile such that at least 1% w/w and no more than 50% w/w of the flibanserin is released at 1 hour;

at least 5% w/w and up to 60% w/w of the flibanserin is released at 4 hours;

at least 35% w/w and up to 95% w/w of the flibanserin is released at 12 hours, when dissolution is measured using a USP (Type II) apparatus.

6. The pharmaceutical release system according to claim 2, characterized by having an in vitro dissolution profile such that at least 1% w/w and no more than 50% w/w of the flibanserin is released at 1 hour;

at least 5% w/w and up to 60% w/w of the flibanserin is released at 4 hours;

at least 35% w/w and up to 95% w/w of the flibanserin is released at 12 hours, when dissolution is measured using a USP (Type II) apparatus.