Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D473/00—Heterocyclic compounds containing purine ring systems
  • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
  • C07D473/16—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms

Definitions

• the present invention relates to crystalline abacavir hydrochloride monohydrate and process for its preparation.
• Abacavir (I) is chemically known as (IS, 4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9- yl]-2-cyclopentene-l -methanol.
• Abacavir sulfate and its combination are used in the treatment of human immunodeficienc virus (HIV) infection.
• HIV human immunodeficienc virus
• patent EP 0349242 Bl discloses 9-substituted-2-amino purines including abacavir, process for preparation and pharmaceutical composition thereof.
• the patent EP 0434450 Bl describes process for preparation of abacavir hydrochloride by reacting abacavir with IN hydrochloric acid in ethanol followed by evaporating the solution to dryness.
• the crude abacavir hydrochloride thus obtained was recrystallized from mixture of ethanol-ethyl acetate to give abacavir hydrochloride 0.8 hydrate.
• the physical or chemical properties of a drug can vary depending on the crystalline form of the drug, and such physical and chemical properties can greatly influence a suitable dosage form of the drug, the optimization of a process for preparing the drug, and the in vivo absorption of the drug.
• the discovery of the most appropriate crystalline form of a drug in a procedure for developing the drug enables the development time and cost to be reduced.
• the present invention relates to crystalline abacavir hydrochloride monohydrate.
• the present invention further provides a process for preparation of crystalline abacavir hydrochloride monohydrate comprising;
• Figure 1 X-ray powder differactogram of crystalline abacavir hydrochloride monohydrate.
• Figure 2 IR spectrum of crystalline abacavir hydrochloride monohydrate.
• crystalline abacavir hydrochloride monohydrate In one embodiment there is provided crystalline abacavir hydrochloride monohydrate.
• the XRPD of crystalline abacavir hydrochloride monohydrate is as shown in figure 1.
• the crystalline abacavir hydrochloride monohydrate is characterized by an infra-red spectrum having major peaks at 3420, 3292, 3087, 1670, 1643 1404, 1217, 10.35 and 762 ⁇ 5 cm "1 .
• the IR spectrum of crystalline abacavir hydrochloride monohydrate is as shown in figure 2.
• the crystalline abacavir hydrochloride monohydrate characterized by thermogravimetric analysis (TGA) showing Delta Y of 5 % which corresponds to the loss of one water molecule.
• TGA thermogravimetric analysis
• the crystalline abacavir hydrochloride monohydrate was found to be stable at 25 ⁇ 2 °C (60 ⁇ 5 RH).
• Abacavir hydrochloride used for crystallization in the present invention may be prepared as per method known in literature.
• the C 1 -C 4 alcoholic solvent is selected from methanol, ethanol, n-propanol, isopropanol and butanol, preferably isopropanol.
• the aqueous C 1 -C 4 alcoholic solvent contains 1 to 20 % of water.
• the quantity of aqueous C 1 -C 4 alcoholic solvent is 5 to 15 times of abacavir hydrochloride.
• the step (a) is carried out by heating which is in the range 40-80 °C, preferably the temperature is between 40-60 °C.
• the solution is optionally filtered.
• the solution is allowed to cool to ambient temperature, then allowed to cool to -10 to 15 °C, more preferably to 0-5 °C.
• Crystalline abacavir hydrochloride can be isolated by methods known in the literature such as filtration, concentration and evaporation etc.
• FTIR spectrum was obtained using a Perkin Elmer Precisely Spectrum 400 instrument using KBr pellet method.
• Thermogravimetric analysis (TGA) was done using Pyris-1 TGA Perkin Elmer instrument. The scans were recorded between 30 and 300 °C at a constant heating rate of 10°C/min.
• Abacavir hydrochloride (70 g) was added in mixture of water (70 ml) and isopropanol (700 ml). The mixture was heated to 50 °C to obtain clear solution. Cooled to 0-5 °C and stirred for 4 hours. The solid was filtered, washed with isopropanol (25 ml) and dried under vacuum. Yield: 50 g, melting point: 126.0-126.8 °C.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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Publications (1)

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Citations (3)

• 2014
  • 2014-09-27 WO PCT/IB2014/064890 patent/WO2015049623A1/en not_active Ceased
  • 2014-09-27 ES ES14793623.1T patent/ES2651854T3/es active Active
  • 2014-09-27 IN IN3145MU2013 patent/IN2013MU03145A/en unknown
  • 2014-09-27 EP EP14793623.1A patent/EP3052499B1/en not_active Not-in-force

Patent Citations (3)

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