EP3148988A1 - Formes polymorphes de la furazidine - Google Patents

Formes polymorphes de la furazidine

Info

Publication number
EP3148988A1
EP3148988A1 EP15753991.7A EP15753991A EP3148988A1 EP 3148988 A1 EP3148988 A1 EP 3148988A1 EP 15753991 A EP15753991 A EP 15753991A EP 3148988 A1 EP3148988 A1 EP 3148988A1
Authority
EP
European Patent Office
Prior art keywords
furazidin
polymorph
crystalline form
polymorphic forms
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.)
Withdrawn
Application number
EP15753991.7A
Other languages
German (de)
English (en)
Inventor
Vilnis LIEPINS
Mikhail SKOMOROKHOV
Nina LUKJANOVA
Evgenij MATIUSHENKOV
Jekaterina REVJUKA
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.)
Olainfarm AS
Original Assignee
Olainfarm AS
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 Olainfarm AS filed Critical Olainfarm AS
Publication of EP3148988A1 publication Critical patent/EP3148988A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • the current invention relates to the field of medical chemistry, namely to the crystalline polymorphic forms of a pharmaceutical industrial product Furazidin and method of preparation thereof.
  • the current invention also relates to the use of said polymorphic forms for the preparation of a pharmaceutical composition.
  • Furazidin (l- ⁇ [(lE,2E)-3-(5-nitrofuran-2-yl)prop-2-ene-l-ylidene]amino ⁇ imidazolidin-2,4- dione) is known at the pharmaceutical market under the trade name Furagin® (Furaginum, INN).
  • This medicament is widely used for the treatment of urinary infections in adults and children.
  • Solid crystalline substances may exist in different crystalline forms, which are called polymorphs.
  • Different polymorphs may possess different physical and/or chemical properties, like solubility, solubility rate, melting temperature, stability etc. These properties may directly affect the possibility of preparation of the active substance and its corresponding pharmaceutical product, as well as stability and bioavailability of that product.
  • polymorphism may affect the quality of a pharmaceutical product, and/or its safety and efficacy.
  • Preparation of a pure polymorph and investigation of its properties provide for a better control of the pharmaceutical product manufacturing process. Controlled and reproducible methods for preparation of pure polymorphs are suitable for industrial application; pure polymorphs may be used for improvement of properties of the pharmaceutical compositions.
  • Furazidin is synthesized by reaction of the 3-(5-nitro-2-furyl)acroleine and 1 -aminohydantoine or 3-(5-nitro-2-furyl)acroleine with semicarbazidacetic acid derivative following with hydantoine cycle formation (J. Pharm. Soc. Japan, 1955, 75; 117, FR1489091, 1966).
  • Several preparation methods of furazidin from 1 -arylaminohydantoines in the presence of mineral acids (sulfuric acid, hydrochloric acid, sulfonic acids) also were disclosed (US 2990402; WO97/19930; WO98/41520). Furazidin polymorphic forms were not described so far.
  • a crystalline form is prepared with admixture of other crystalline forms, it may result in the instability of a dosage form during manufacturing process and its conversion into another polymorphic form. Therefore, it is very important to obtain polymorphic forms of a high polymorphic purity.
  • Polymorph II characteristic XRPD pattern is represented at Fig.3. Diffraction pattern peaks position and its relative intensity are summarized in the Table 1. Peaks position 2 ⁇ angles are presented as ⁇ 0.2°. IR spectrum of the Polymorph II is represented at Fig.4.
  • pure Furazidin polymorphs I and II may be obtained by 3- (5-nitrofuran-2-yl)acroleine condensation with 1 -aminohydantoine in the presence of the required polymorph crystal seeds.
  • polymorph I or polymorph II are obtained with polymorphic purity of over 90%. If said condensation reaction is performed without crystal seeds, Polymorph I or a mixture of Polymorph I and Polymorph II is usually obtained.
  • Polymorph II dissolves better than Polymorph I.
  • the dissolution dynamics of the Polymorph II is also substantially better than of Polymorph I.
  • Faster dissolution may positively affect the bioavailability of the pharmaceutical substance upon dissolution of a dosage form in a body.
  • Polymorph I and II characteristic DSC curves are shown at Fig. 8 and 9 and it reveals a difference between two polymorphs.
  • Polymorph II curve demonstrates an exothermic effect with a maximum at 212 °C, which corresponds to the form II turning into from I.
  • Polymorphs obtained according to the current invention, are suitable to prepare pharmaceutical compositions.
  • a pharmaceutical composition comprising a polymorph of Furazidin, according to the current invention, is suitable for use as an antibacterial medicament.
  • XRPD XRPD were recorded using Bruker D8 Advance apparatus equipped with LynxEye position-sensitive detector. Recording mode: 3-35 0 2 ⁇ , speed 0.2s/0.02 °. Samples were powdered in an agate mortar prior to analysis.
  • Differencing scanning calorimetry curves were recorded using Mettler TA 4000 calorimeter according to the manufacturer's instructions. DSC curves were recorded at a temperature range from 50 °C to 250 °C with heating rate of 5.0 °C/min in the nitrogen atmosphere.
  • 3-(5-Nitrofuran-2-yl)acroleine 45 g was placed into 2 L three-neck flask equipped with stirrer, thermometer and reflux condenser and isopropanol (750 mL), water (150 mL) and acetic acid (15 mL) were added thereto. Reaction mixture was stirred at 60-80 °C until 3-(5-nitrofuran-2- yl)acroleine was completely dissolved.
  • Furazidin Polymorph II seed crystals (3 g) were added to the warm solution of 3-(5-nitrofuran-
  • Polymorph I was obtained similarly to the Polymorph II as described in the Example 1, but optionally adding the Polymorph I seed crystals.
  • Furazidin sample for analysis (0.05 g) was placed in a capsule No.3.
  • a solid dosage form dissolution apparatus equipped with the stirrer and the capsule immersion helping device was used.
  • 900 mL of sodium hydrogen carbonate 1.5% water solution was used as a solution media.
  • the solution was heated to 37 ⁇ 0.5 °C.
  • One capsule was placed in each vessel using immersion device and the apparatus was turned on.
  • Solution aliquots were taken, cooled down and filtered through a paper filter, discarding the first portion of the filtrate.
  • Filtrate (5.0 mL) was placed in the 50 mL measuring flask and diluted with 1.5% sodium hydrogen carbonate solution to the mark level and well stirred.
  • Light absorption maximum of the analyzed solution was measured using Agilent 8453 No. CN22805904 spectrophotometer at wavelength of 410 ⁇ 2 nm relatively to the absorption of the standard sample. From the obtained data dissolution curves were drawn.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Communicable Diseases (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Oncology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

L'invention concerne les formes cristallines de la furazidine (1-{[(1E,2E)-3-(5-nitrofuran-2-yl)prop-2-ène-1-ylidène]amino}imidazolidine-2,4-dione) et des procédés de préparation de celles-ci.
EP15753991.7A 2014-05-29 2015-05-27 Formes polymorphes de la furazidine Withdrawn EP3148988A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
LVP-14-44A LV15081B (lv) 2014-05-29 2014-05-29 Furazidīna polimorfās formas
PCT/IB2015/053968 WO2015181741A1 (fr) 2014-05-29 2015-05-27 Formes polymorphes de la furazidine

Publications (1)

Publication Number Publication Date
EP3148988A1 true EP3148988A1 (fr) 2017-04-05

Family

ID=53969380

Family Applications (1)

Application Number Title Priority Date Filing Date
EP15753991.7A Withdrawn EP3148988A1 (fr) 2014-05-29 2015-05-27 Formes polymorphes de la furazidine

Country Status (6)

Country Link
EP (1) EP3148988A1 (fr)
EA (1) EA201692217A1 (fr)
LV (1) LV15081B (fr)
MA (1) MA39860A (fr)
UA (1) UA115290C2 (fr)
WO (1) WO2015181741A1 (fr)

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2990402A (en) 1958-10-07 1961-06-27 Smith Kline French Lab Preparation of 1-aminohydantoin derivatives
FR1489091A (fr) 1966-05-09 1967-07-21 Clin Byla Ets Nouvelles hydantoïnes et leur préparation
WO1997019930A1 (fr) 1995-11-27 1997-06-05 Lonza Ag Procede de production de 1-aminohydantoine
PL185120B1 (pl) 1997-03-17 2003-02-28 Adamed Sp Z Oo Sposób┴wytwarzania┴1-{[3-(5-nitro-2-furylo)-2-propenylideno]-amino}-2,4-imidazolidynodionu

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
None *
See also references of WO2015181741A1 *

Also Published As

Publication number Publication date
LV15081A (lv) 2015-12-20
WO2015181741A1 (fr) 2015-12-03
UA115290C2 (uk) 2017-10-10
LV15081B (lv) 2016-11-20
EA201692217A1 (ru) 2017-05-31
MA39860A (fr) 2015-12-03

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