ITMI20071594A1 - Forma cristallina monoidrata di adefovir dipivoxil - Google Patents

Forma cristallina monoidrata di adefovir dipivoxil Download PDF

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Publication number
ITMI20071594A1
ITMI20071594A1 IT001594A ITMI20071594A ITMI20071594A1 IT MI20071594 A1 ITMI20071594 A1 IT MI20071594A1 IT 001594 A IT001594 A IT 001594A IT MI20071594 A ITMI20071594 A IT MI20071594A IT MI20071594 A1 ITMI20071594 A1 IT MI20071594A1
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IT
Italy
Prior art keywords
adefovir dipivoxil
crystalline form
monohydrate
monohydrate crystalline
adefovir
Prior art date
Application number
IT001594A
Other languages
English (en)
Original Assignee
Solmag Spa
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 Solmag Spa filed Critical Solmag Spa
Priority to IT001594A priority Critical patent/ITMI20071594A1/it
Priority to US12/671,556 priority patent/US8389722B2/en
Priority to JP2010518565A priority patent/JP2010535164A/ja
Priority to EP08785262A priority patent/EP2176275A1/en
Priority to CA2695660A priority patent/CA2695660A1/en
Priority to PCT/EP2008/006320 priority patent/WO2009015892A1/en
Priority to KR1020107002326A priority patent/KR20100045986A/ko
Publication of ITMI20071594A1 publication Critical patent/ITMI20071594A1/it

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
    • C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
    • 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
    • A61P31/12—Antivirals
    • 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
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • 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
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • 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
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Virology (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • AIDS & HIV (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)

Description

Descrizione del brevetto per invenzione industriale avente per titolo:
“FORMA CRISTALLINA MONOIDRATA DI ADEFOVIR DIPIVOXIL”
La presente invenzione ha per oggetto una nuova forma cristallina monoidrata di Adefovir Dipivoxil, un processo per la sua preparazione e composizioni farmaceutiche contenenti detta forma monoidrata.
Stato della tecnica
Adefovir Dipivoxil è un noto inibitore nucleotidico della trascrittasi inversa impiegato in clinica per il trattamento di infezioni da retro-virus, in particolare HIV e HBV (US 5,663,159).
WO 99/04774 e US 6,451,340 descrivono forme cristalline di Adefovir ed in particolare la forma cristallina 1 (anidra) e la forma cristallina 2 (biidrata KF = 6,7%).
Le due forme cristalline sono state preparate e caratterizzate. Le analisi della Forma 1 sono riportate nelle Figure 1-3 mentre le analisi della Forma 2 sono riportate nelle Figure 4-6.
WO 00/35460 descrive formulazioni farmaceutiche comprendenti adefovir dipivoxil anidro e diidrato e un eccipiente alcalino.
Descrizione dell’invenzione
Si è ora trovata una nuova forma cristallina monoidrata di Adefovir Dipivoxil che risulta vantaggiosa nell’impiego farmaceutico rispetto alle note forme amorfa e cristalline.
La forma monoidrata oggetto dell’invenzione presenta un contenuto di acqua misurato al Karl Fischer compreso tra il 3% e il 5% e le analisi DSC, lo spettro IR e di diffrazione ai raggi X riportati nelle Figure 7-9.
L’invenzione riguarda anche formulazioni farmaceutiche contenenti la nuova forma cristallina monoidrata di Adefovir Dipivoxil.
La nuova forma oggetto dell’invenzione è ottenuta per evaporazione spontanea del solvente di cristallizzazione in condizioni controllate. Tale evaporazione può essere effettuata a pressione ridotta oppure lasciando il prodotto a una temperatura ambiente di 20-25°C per almeno 24 ore, in condizioni di umidità ambiente o in atmosfera satura umida.
L’invenzione è descritta in maggior dettaglio nel seguente esempio. ESEMPIO
Adefovir Dipivoxil è stato preparato seguendo il brevetto US 5,663,159, esempio 9. Si ottengono 25 g di prodotto che vengono sciolti in 70 mi di cloruro di metilene e 1 mi di metanolo.
Si impacca una colonna cromatografica con 12 g di silice. La soluzione del prodotto viene caricata in colonna ed eluita con altri 600 mi di cloruro di metilene.
Il prodotto viene quindi evaporato a secco in vacuo ottenendo 25 g di Adefovir dipivoxil avente un KF tra il 3% e il 5% e che risulta essere un monoidrato.
Lo stesso prodotto è stato ottenuto per evaporazione spontanea del solvente a temperatura e umidità ambiente per almeno 24 ore o per evaporazione spontanea del solvente a 25°C in atmosfera umida satura per 24 ore.
L’analisi DSC, lo spettro IR e i raggi X del monoidrato sono riportati nelle Figure 7-9. Come paragone sono riportati anche i corrispondenti DSC, IR, e RX della forma anidra e della forma diidrata, prodotte come descritto in WO 99/04774 e US 6,451,340.

Claims (3)

  1. RIVENDICAZIONI 1. Adefovir Dipivoxil monoidrato cristallino.
  2. 2. Adefovir Dipivoxil monoidrato cristallino secondo la rivendicazione 1 avente un contenuto di acqua misurato al Karl Fischer compreso tra il 3% e il 5% e analisi DSC, spettro IR e di diffrazione ai raggi X riportati nelle Figure 7-9.
  3. 3. Composizioni farmaceutiche comprendenti come ingrediente attivo Adefovir Dipivoxil monoidrato cristallino delle rivendicazioni 1-2.
IT001594A 2007-08-02 2007-08-02 Forma cristallina monoidrata di adefovir dipivoxil ITMI20071594A1 (it)

Priority Applications (7)

Application Number Priority Date Filing Date Title
IT001594A ITMI20071594A1 (it) 2007-08-02 2007-08-02 Forma cristallina monoidrata di adefovir dipivoxil
US12/671,556 US8389722B2 (en) 2007-08-02 2008-07-31 Adefovir dipivoxil crystalline monohydrate form
JP2010518565A JP2010535164A (ja) 2007-08-02 2008-07-31 アデホビルジピボキシルの結晶性一水和物型
EP08785262A EP2176275A1 (en) 2007-08-02 2008-07-31 Adefovir dipivoxil crystalline monohydrate form
CA2695660A CA2695660A1 (en) 2007-08-02 2008-07-31 Adefovir dipivoxil crystalline monohydrate form
PCT/EP2008/006320 WO2009015892A1 (en) 2007-08-02 2008-07-31 Adefovir dipivoxil crystalline monohydrate form
KR1020107002326A KR20100045986A (ko) 2007-08-02 2008-07-31 아데포비르 디피복실 결정형 일수화물 형태

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
IT001594A ITMI20071594A1 (it) 2007-08-02 2007-08-02 Forma cristallina monoidrata di adefovir dipivoxil

Publications (1)

Publication Number Publication Date
ITMI20071594A1 true ITMI20071594A1 (it) 2009-02-03

Family

ID=40039990

Family Applications (1)

Application Number Title Priority Date Filing Date
IT001594A ITMI20071594A1 (it) 2007-08-02 2007-08-02 Forma cristallina monoidrata di adefovir dipivoxil

Country Status (7)

Country Link
US (1) US8389722B2 (it)
EP (1) EP2176275A1 (it)
JP (1) JP2010535164A (it)
KR (1) KR20100045986A (it)
CA (1) CA2695660A1 (it)
IT (1) ITMI20071594A1 (it)
WO (1) WO2009015892A1 (it)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011016044A1 (en) * 2009-08-03 2011-02-10 Hetero Research Foundation Novel polymorphs of adefovir dipivoxil
UA116825C2 (uk) 2013-11-15 2018-05-10 Чимерикс Інк. Морфологічні форми гексадецилоксипропілових складних ефірів фосфонової кислоти і способи їх синтезу
CN104387421B (zh) * 2014-11-27 2016-04-06 苏州二叶制药有限公司 阿德福韦酯一水合物及其制备方法

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK0481214T3 (da) * 1990-09-14 1999-02-22 Acad Of Science Czech Republic Prolægemidler af phosphonater
ES2187991T3 (es) * 1997-07-25 2003-06-16 Gilead Sciences Inc Composiciones de analogo de nucleotido.
ZA986614B (en) * 1997-07-25 1999-01-27 Gilead Sciences Nucleotide analog composition
TWI230618B (en) 1998-12-15 2005-04-11 Gilead Sciences Inc Pharmaceutical compositions of 9-[2-[[bis[(pivaloyloxy)methyl]phosphono]methoxy]ethyl]adenine and tablets or capsules containing the same
CN1935818B (zh) * 2006-09-22 2011-11-09 闫敬武 阿德福韦酯新晶态、晶态组合物、制备方法及应用
US7935817B2 (en) * 2008-03-31 2011-05-03 Apotex Pharmachem Inc. Salt form and cocrystals of adefovir dipivoxil and processes for preparation thereof
KR20100031045A (ko) * 2008-09-11 2010-03-19 씨제이제일제당 (주) 아데포비어 디피복실의 정제방법
CN102365283B (zh) * 2009-03-26 2014-04-09 株式会社大熊制药 阿德福韦酯的新晶型及其制备方法

Also Published As

Publication number Publication date
KR20100045986A (ko) 2010-05-04
US20100292470A1 (en) 2010-11-18
EP2176275A1 (en) 2010-04-21
JP2010535164A (ja) 2010-11-18
WO2009015892A1 (en) 2009-02-05
US8389722B2 (en) 2013-03-05
CA2695660A1 (en) 2009-02-05

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