WO2014167575A2 - Composition stable de tigécycline - Google Patents

Composition stable de tigécycline Download PDF

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Publication number
WO2014167575A2
WO2014167575A2 PCT/IN2014/000186 IN2014000186W WO2014167575A2 WO 2014167575 A2 WO2014167575 A2 WO 2014167575A2 IN 2014000186 W IN2014000186 W IN 2014000186W WO 2014167575 A2 WO2014167575 A2 WO 2014167575A2
Authority
WO
WIPO (PCT)
Prior art keywords
tigecycline
pharmaceutical composition
maltose
stable pharmaceutical
solution
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IN2014/000186
Other languages
English (en)
Other versions
WO2014167575A3 (fr
Inventor
Dhara PARIKH
Aditya Patel
Pallerla Bhaskar
Ashish Sehgal
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Astron Research Ltd
Original Assignee
Astron Research Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Astron Research Ltd filed Critical Astron Research Ltd
Priority to US14/779,889 priority Critical patent/US9511145B2/en
Priority to PL14782395T priority patent/PL2978426T3/pl
Priority to SI201431458T priority patent/SI2978426T1/sl
Priority to ES14782395T priority patent/ES2766832T3/es
Priority to EP14782395.9A priority patent/EP2978426B1/fr
Priority to CA2905645A priority patent/CA2905645C/fr
Publication of WO2014167575A2 publication Critical patent/WO2014167575A2/fr
Publication of WO2014167575A3 publication Critical patent/WO2014167575A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/65—Tetracyclines

Definitions

  • the present invention relates to a stable pharmaceutical composition comprising Tigecycline and maltose. Further the present invention discloses process for the preparation of the said composition.
  • Tigecycline is a tetracycline derivative (a glycylcycline) which is a chemically (4S,4aS,5aR,12aS)-9-[2-(tert-butylamino)acetamido]-4,7bis(dimethylamino)- I.,4,4a,5,5a,6, 11,12a-octahydro-3, 10,12,12a-tetrahydroxy- 1,11 -dioxo-2- naphthacenecarboxamide.
  • Molecular formula of Tigecycline is C29H39N5OS a
  • USRE40I83 discloses 7-substituted-9-substituted amino-6-demethyl-6- deoxytetracyclines which cover Tigecycline.
  • Tigecycline is marketed as lyophilized powder for reconstitution for intravenous infusion under trade name TYGACIL® by Wyeth; which contains Tigecycline as active ingredient and lactose monohydrate as inactive ingredient.
  • Tigecycline is approved for complicated skin and skin structure infections, complicated intra-abdominal infections and community-acquired bacterial pneumonia.
  • Tigecycline is currently marked as TYGAC!L® by Wyeth; which contains lactose monohydrate as inactive ingredient.
  • the pH of the composition after reconstitution is acidic.
  • the composition uses lactose monohydrate as stabilizer to control the degradation of Tigecycline by epimerization pathways.
  • US7879828 discloses a composition comprising tigecycline, lactose, and an acid •selected from hydrochloric acid and gentisic acid, and the pH of the composition in a solution is between about 3.0 and about 7.0. Focus of US7879828 is to use lactose and lower pH to get stable composition of Tigecycline.
  • US7705168 discloses a manufacturing process for the production of tigecycline as a reconstitutable powder having less than 0.9% total degradants comprising the steps of reducing and maintaining the oxygen level in water for injection to less than or equal to 0.5 ppm. Focus of US7705I68 is to control oxidation0 pathway by controlling oxygen level.
  • US2009275660 discloses stable parenteral formulations of tigecycline and process of preparation thereof, wherein the formulation comprises of an edetate, a pH modifying agent or an antioxidant, such that the formulation remains stable5 for at least 45 hours. Focus of US2009275660 is to provide stable composition by using edetate.
  • US2010035845 discloses a frozen pharmaceutical formulation suitable for administration to a subject parenteraily, comprising a therapeutically effective0 amount of tigecycline and an agent selected from the group consisting of lactose, dextrose, glucose, mannose, sucrose, ribose, xylose and a combination thereof. Focus of US201 0035845 is to use lactose, dextrose, glucose, mannose, sucrose, ribose, xylose to get stable composition of Tigecycl ine.
  • the present invention relates to a stable pharmaceutical composition
  • a stable pharmaceutical composition comprisi ng Tigecycl ine and maltose.
  • Another object of the present invention is to provide process for the preparation of a stable pharmaceutical composition comprising Tigecycl ine and maltose.
  • Another object of the present invention is to provide a stable pharmaceutical composition
  • a stable pharmaceutical composition comprising Tigecycl ine and maltose wherei n the pH of the composition after reconstitution is in between 3 - 6 preferably between 4 - 5 and more preferably between 4.3 - 4.9.
  • Another object of the present invention is to provide a stable pharmaceutical composition comprising Tigecycl ine and maltose wherein the composition is prepared from bulk solution comprises Tigecycl ine from 1 5 - 50 mg/mL, maltose from 30 - 1 00 mg/mL and pH of the bu lk solution is in between 3 - 6, preferably between 4 - 5 and more preferably between 4.3 - 4.9.
  • Another object of the present invention is to provide process for preparation of a stable pharmaceutical composition comprising Tigecycl ine and maltose wherein the pH o f the composition after reconstitution is in between 3 - 6 preferably between 4 - 5 and more preferably between 4.3 - 4.9.
  • Another object of the present invention is to disclose use of maltose as stabilizing agent for preparation of stable Tigecycline composition.
  • Present invention provides a stable pharmaceutical composition comprising Tigecycline and maltose. Further the invention provides a use of maltose as stabilizing agent for preparation of stable Tigecycline composition. In another embodiment the present invention provides a process for preparation of stable pharmaceutical composition comprising Tigecycline and maltose. In one another embodiment the present invention also provides a stable pharmaceutical composition comprising Tigecycline and maltose wherein the pH of the composition after reconstitution is in between 3-6.
  • Present invention provides a stable pharmaceutical composition comprising Tigecycline and maltose and a process for the preparation of the said composition.
  • the stable pharmaceutical composition comprises Tigecyciine and maltose; wherein the composition is prepared from bulk solution comprises Tigecycline from 15 - 50 mg/mL. maltose from 30 - 100 mg/mL and pH of the bulk solution is in between 3-6.
  • a stable pharmaceutical composition is defined as a lyophilized composition comprising Tigecycline and maltose; wherein impurity 4-epimer of Tigecycline, is less than 3% throughout shelf life.
  • 4-epimer of Tigecycline is having following structure:
  • the stable pharmaceutical composition of the present invention is analyzed by HPLC method.
  • the method of analysis by HPLC is well known in the art.
  • a bulk solution is defined as a solution comprising Tigecycline and maltose, which is further lyophilized to obtain a stable pharmaceutical composition according to the present invention.
  • the pH of the bulk solution is in between 3 - 6, wherein pH is attained by addition of pH adjusting agents like NaOH or HCI.
  • Lyophilization also known as freeze drying, is a process in which solvent is removed from a bulk solution after it is frozen and placed under a vacuum, allowing the solvent to change directly from solid to gaseous phase without passing through a liquid phase. Lyophilization process is well known to the person skilled in the art.
  • desired dissolved oxygen (DO) level refers to low amount of dissolved oxygen in solvent, preferably in the range of 0.5 ppm to 2 ppm.
  • the present invention provides a process for the preparation of a stable pharmaceutical composition comprising Tigecycline and maltose comprising step of:
  • step I 1. Taking WFI in manufacturing tank, sparging inert gas until desired dissolved oxygen level is attained. 2. Adding Maltose and Tigecycline to the solution of step I. in any order and adjusting pH of the solution in between 3 - 6.
  • a process for preparation of a stable pharmaceutical composition comprising step of adding maltose and Tigecycline to the water for injection (WFI) in any order and adjusting pfl of the solution in between 3 -6.
  • a process for preparation of a stable pharmaceutical composition comprising a step of adding maltose and Tigecycline to the water for injection (WFI) in any order; wherein Hydrochloric acid is added prior to the addition Tigecycline.
  • WFI water for injection
  • the present invention provides a process for the preparation of a stable pharmaceutical composition comprising Tigecycline and ' maltose comprising step of:
  • step 2 2. Adding Maltose to the solution of step 1 and stir.
  • the present invention provides a stable pharmaceutical composition comprising Tigecycline and maltose wherein the pH of the composition after reconstitution is in between 3-6 preferably between 4-5 and more preferably between 4.3 - 4.9 and process for preparation of the same.
  • the present invention discloses use of maltose as stabilizing agent for preparation of stable Tigecycline composition.
  • Example 1 Composition of Tigecycline bulk solution:
  • step 2 2. Adding Maltose and Tigecycline to the solution of step 1 in any order.
  • Example 2 Composition of Tigecycline bulk solution:
  • pH of the bulk / reconstituted solution is approx.4.7.
  • step II 2. Adding Maltose to the solution of step I and stir.
  • Lyophilized product obtained according to example 1 and 2 comprises of Tigecycline and maltose; wherein the pH of the composition after reconstitution is in between 3-6.
  • Stability study The stability study of the composition obtained by example 2 was carried out at 25°C and 60% RH, 40°C and 75% RH and 50°C for 1 month. The results obtained in the stability study are given below:

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne une composition pharmaceutique stable de Tigécycline et un procédé de préparation de celle-ci. La composition comprend de la Tigécycline et du maltose, le pH de la solution principale ou de la solution après reconstitution se situant entre 3 et 6.
PCT/IN2014/000186 2013-03-26 2014-03-25 Composition stable de tigécycline Ceased WO2014167575A2 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
US14/779,889 US9511145B2 (en) 2013-03-26 2014-03-25 Stable tigecycline composition
PL14782395T PL2978426T3 (pl) 2013-03-26 2014-03-25 Stabilna kompozycja tygecykliny
SI201431458T SI2978426T1 (sl) 2013-03-26 2014-03-25 Stabilni sestavek tigeciklina
ES14782395T ES2766832T3 (es) 2013-03-26 2014-03-25 Composición estable de tigeciclina
EP14782395.9A EP2978426B1 (fr) 2013-03-26 2014-03-25 Composition stable de tigécycline
CA2905645A CA2905645C (fr) 2013-03-26 2014-03-25 Composition stable de tigecycline

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
INMU11272013 2013-03-26
IN1127/MUM/2013 2013-03-26

Publications (2)

Publication Number Publication Date
WO2014167575A2 true WO2014167575A2 (fr) 2014-10-16
WO2014167575A3 WO2014167575A3 (fr) 2014-12-24

Family

ID=51690086

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2014/000186 Ceased WO2014167575A2 (fr) 2013-03-26 2014-03-25 Composition stable de tigécycline

Country Status (1)

Country Link
WO (1) WO2014167575A2 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090275660A1 (en) 2008-05-01 2009-11-05 Chauhan Bhaskar Stable parenteral formulations of tigecycline
US20100035845A1 (en) 2008-08-06 2010-02-11 Wyeth Tigecycline formulations
US7705168B2 (en) 2005-06-16 2010-04-27 Wyeth Llc Manufacturing process for tigecycline
US7879828B2 (en) 2005-03-14 2011-02-01 Wyeth Llc Tigecycline compositions and methods of preparation
WO2011143503A2 (fr) 2010-05-12 2011-11-17 Rempex Pharmaceuticals, Inc. Compositions de tétracycline

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100197650A1 (en) * 2008-08-28 2010-08-05 Forest Laboratories Holdings Ltd. Compositions and methods of treatment comprising ceftaroline

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7879828B2 (en) 2005-03-14 2011-02-01 Wyeth Llc Tigecycline compositions and methods of preparation
US7705168B2 (en) 2005-06-16 2010-04-27 Wyeth Llc Manufacturing process for tigecycline
US20090275660A1 (en) 2008-05-01 2009-11-05 Chauhan Bhaskar Stable parenteral formulations of tigecycline
US20100035845A1 (en) 2008-08-06 2010-02-11 Wyeth Tigecycline formulations
WO2011143503A2 (fr) 2010-05-12 2011-11-17 Rempex Pharmaceuticals, Inc. Compositions de tétracycline

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP2978426A4

Also Published As

Publication number Publication date
WO2014167575A3 (fr) 2014-12-24

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