Amorphous and crystalline forms of losartan potassium and process for their preparation
AssigneeTeva Pharmaceutical Industries Ltd.
InventorsBen Zion Dolitzky, Shlomit Wizel, Gennady Nisnevich, Igor Rukhman, Julia Kaftanov
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Abstract
This invention relates to novel amorphous losartan potassium, novel losartan potassium in a crystalline form that is a hydrate, novel crystalline losartan potassium Form IV and solvates thereof, novel crystalline losartan potassium Form V and solvates thereof, to processes for their preparation, to compositions containing them and to their use in medicine. This invention further relates to a novel process for preparing crystalline losartan potassium Form I and Form II.
Claims81
Amorphous losartan potassium.
A process for preparing amorphous losartan potassium comprising the steps of:
- dissolving losartan potassium in a solvent to form a solution, and
- removing the solvent from the solution to afford amorphous losartan potassium
Losartan potassium in a crystalline form that is a hydrate.
Losartan potassium in a crystalline form characterized by a powder x-ray diffraction pattern with peaks at about 5.7, 8.9, 13.3, 17.5, 20.0, and 21.1±0.2 degrees two-theta.
A process for preparing losartan potassium in a crystalline form that is a hydrate comprising the step of:
- exposing amorphous losartan potassium or losartan potassium Form I to an atmosphere having a relative humidity greater than about 60%.
Losartan potassium Form IV and solvates thereof.
Losartan potassium in a crystalline form and solvates thereof characterized by a powder x-ray diffraction pattern with peaks at about 4.3, 15.6, and 23.4±0.2 degrees two-theta.
Losartan potassium in a crystalline form and solvates thereof having a differential scanning calorimetric thermogram with endothermic peaks at about 78° C., 218° C., 240° C., and 255° C.
A process for preparing losartan potassium and solvates thereof having at least one characteristic of Form IV comprising the steps of:
- providing a solution of losartan potassium in a solvent to form a solution, the solvent being characterized as having a boiling point of about 135° C. or below,
- adding methylene chloride to the solution whereby a suspension is formed, and
- isolating losartan potassium Form IV.
Losartan potassium Form V and solvates thereof.
Losartan potassium in a crystalline form and solvates thereof characterized by a powder x-ray diffraction pattern with peaks at about 6.4, 12.2, 20.7, 21.5, and 22.5±0.2 degrees two-theta.
A process for preparing losartan potassium and solvates thereof having at least one characteristic of Form V comprising the steps of:
- providing a solution of losartan potassium in a solvent to form a solution, the solvent being characterized as having a boiling point of about 135° C. or below,
- adding hexane to form a mixture, and
- isolating losartan potassium Form V.
A process for preparing losartan potassium Form II comprising the steps of:
- providing a solution of losartan potassium in a solvent to form a solution, the solvent being characterized by its capacity to solubilize losartan potassium at room temperature at a concentration up to at least about 0.1 gram per milliliter of solvent and as having a boiling point of about 135° C. or below,
- adding the solution to xylene to form a mixture,
- evaporating the solvent from the mixture, and
- isolating losartan potassium Form II.
A process for preparing losartan potassium Form I comprising the steps of:
- (a) providing a solution of losartan potassium in a first solvent to form a solution, the solvent being characterized as having a boiling point of about 135° C. or below,
- (b) reducing the temperature of the solution, and
- (c) isolating losartan potassium Form I.
A process for preparing losartan potassium Form I comprising the steps of:
- providing a solution losartan potassium in a first solvent to form a solution, the solvent being characterized as having a boiling point of about 135° C. or below,
- reducing the temperature of the solution,
- adding to the solution a second solvent selected from the group consisting of ethyl acetate, toluene, acetone, methylethyl ketone, methylene chloride, acetonitrile, dimethyl carbonate, and hexane whereby a suspension is formed,
- and isolating losartan potassium Form I.
A process for preparing losartan potassium Form I comprising the step of:
- heating losartan potassium Form III.
Dependencies are inferred from the claim text.