Pharmaceutical composition with bisphosphonate
OwnerKaren Beltz, Philipp Lustenberger +1inventors
InventorsKaren Beltz, Philipp Lustenberger, Holger Petersen
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Abstract
The present invention relates to depot formulations comprising a poorly water soluble salt of a bisphosphonate forming together with one or more biocompatible polymers, to poorly water-soluble salts of such bisphosphonates, to crystalline forms of the free compounds and the salts and to other related aspects, where the compounds are of the Formula (I), where R1 and R2 are as described in the specification. Compounds of the Formula (I) and their forms mentioned in the disclosure are useful for the treatment of bone-related disorders and cancer.
Claims17
A depot formulation, this term including an implant, comprising a poorly water soluble salt of a bisphosphonate compound of formula I:
- wherein one of R1 and R2 is hydrogen and the other is C1-C5-alkyl that is branched or unbranched in the form of a poorly water-soluble salt;
- and a polymer matrix.
A poorly water-soluble salt of a compound of the formula I,
- wherein one of R1 and R2 is hydrogen and the other is C1-C5-alkyl that is branched or unbranched in the form of a poorly water-soluble salt, in free or solvate form.
A crystalline form of a compound of the formula I
- wherein one of R1 and R2 is hydrogen and the other is C1-C5-alkyl that is branched or unbranched in free form or in the form of a poorly water-soluble salt, in free or solvate form, selected from the group of crystal forms defined as follows:
- a crystalline form of the free zwitterionic form of [2-(5-ethyl-imidazol-1-yl)-1-hydroxy-1-phosphono-ethyl]-phosphonic acid, which has an X-ray powder diffraction pattern with at least one, two, three, or all of the following peaks at an angle of refraction 2 theta (θ) of 10.5, 13.1, 14.7, 17.2, 23.5, 25.2, 34.4, each±0.2;
- alternatively, at least 80% by weight of compound A in the free zwitterionic form shows such X-ray powder diffraction pattern;
- a crystalline form of the calcium salt of [2-(5-ethyl-imidazol-1-yl)-1-hydroxy-1-phosphono-ethyl]-phosphonic acid with a stoichiometry of one calcium and two molecules of compound A, which has an X-ray powder diffraction pattern with at least one, two, three, or all of the following peaks at an angle of refraction 2 theta (θ) of 7.9, 10.6, 12.1, 25.7, 27.4, 29.2, each±0.2;
- alternatively, at least 80% by weight of the calcium 1:2 salt of compound A shows such X-ray powder diffraction pattern;
- a crystalline form of the zinc salt of [2-(5-ethyl-imidazol-1-yl)-1-hydroxy-1-phosphono-ethyl]-phosphonic acid with a stoichiometry of one zinc and two molecules of compound A, which has an X-ray powder diffraction pattern with at least one, two, three, or all of the following peaks at an angle of refraction 2 theta (θ) of 6.7, 9.5, 12.5, 17.7, 27.3, each±0.2;
- alternatively, at least 80% by weight of the zinc 1:2 salt of compound A shows such X-ray powder diffraction pattern;
- and
- a crystalline form of the magnesium salt of [2-(5-ethyl-imidazol-1-yl)-1-hydroxy-1-phosphono-ethyl]-phosphonic acid with a stoichiometry of one magnesium and two molecules of compound A, which has an X-ray powder diffraction pattern with at least one, two, three, or all of the following peaks at an angle of refraction 2 theta (θ) of 6.7, 12.5, 20.0, 27.3, each±0.2;
- alternatively, at least 80% by weight of the magnesium 1:2 salt of compound A shows such X-ray powder diffraction pattern.
Dependencies are inferred from the claim text.