Crystalline forms of valacyclovir hydrochloride
AssigneeTeva Pharmaceutical Industries Ltd.
InventorsShlomit Wizel, Judith Aronhime, Valerie Niddam-Hildesheim, Ben-Zion Dolitzky, Marina Yu Etinger, Michael Yuzefovich, Gennady A. Nisnevich, Boris Pertsikov, Boris Tishin, Dina Blasberger
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Abstract
Provided are novel polymorphs and pseudopolymorphs of valacyclovir hydrochloride and pharmaceutical compositions containing these. Also provided are methods for making the novel polymorphs and pseudopolymorphs, which include valacyclovir hydrochloride monohydrate and valacyclovir hydrochloride dihydrate.
Claims64
Valacyclovir hydrochloride form I.
Valacyclovir hydrochloride sesquihydrate.
Valacyclovir hydrochloride form II.
Valacyclovir hydrochloride form IV.
15 Valacyclovir hydrochloride in form IV of claim 14 further characterized by x-ray diffraction reflections at about 7.2°, 8.6°, 9.5°, 13.3°, 15.2°, 27.3°, and 28.1°±0.2° 2θ.
Valacyclovir hydrochloride form V.
Valacyclovir hydrochloride in form VI.
Valacyclovir hydrochloride in form VII.
A method of making valacyclovir hydrochloride form I comprising the step of slurrying valacyclovir hydrochloride in a slurry solvent selected from the group consisting of ethyl acetate, acetone, methyl ethyl ketone, dioxane, methylene chloride, t-butyl methyl ether, and tetrahydrofurane.
A method of making valacyclovir hydrochloride form II comprising the step of slurrying valacyclovir hydrochloride in a slurry solvent selected from the group consisting of isopropyl alcohol, 1-butanol, and ethanol.
A method of making valacyclovir hydrochloride form II comprising the steps of:
- a, slurrying valacyclovir in a slurry solvent selected from acetonitrille, methyl ethyl ketone, ethyl acetate, acetone, and toluene
- b, heating the slurry to reflux,
- c, refluxing the resulting mixture, and
- d, isolating valacyclovir hydrochloride in form II from the mixture.
A method of making valacyclovir in form III comprising the step of incubating valacyclovir hydrochloride in an atmosphere saturated with vapors of at least one incubating solvent selected from the group consisting of isopropanol, ethanol, butanol, acetone, ethyl acetate, tetrahydrofurane, acetonitrile, and methanol.
A method of making valacyclovir hydrochloride form IV comprising the step of incubating valacyclovir hydrochloride in an atmosphere saturated with vapors of an incubating solvent that is water.
A method of making valacyclovir hydrochloride in form V comprising the step of mixing a solution of valacyclovir hydrochloride in water with a lower aliphatic alcohol.
A method of making valacyclovir in form VI comprising the step of mixing a solution of valacyclovir hydrochloride in a first solvent comprising water and an aliphatic monocarboxylic acid, with a second solvent comprising a water-miscible ketone to form a suspension.
A method of making valacyclovir in form VII comprising the step of mixing a solution of valacyclovir hydrochloride in a first solvent consisting essentially of water with a second solvent comprising a water-miscible ketone to form a suspension.
A method of making valacyclovir hydrochloride in form I comprising the steps of dissolving valacyclovir hydrochloride in a solvent, and evaporating the solution at a reduced pressure.
Valacyclovir hydrochloride monohydrate.
A method of making valacyclovir monohydrate comprising the step of contacting a solution of valacyclovir hydrochloride in water with iso-propanol to form a suspension.
A pharmaceutical composition comprising at least one of valacyclovir hydrochloride in Forms I, II, IV, V, VI or VII.
Valacyclovir hydrochloride dihydrate.
Dependencies are inferred from the claim text.