Stable crystalline form of bifeprunox mesylate (7-[4-([1,1'-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate)
AssigneeSolvay Pharmaceuticals GmbH
InventorsIrene Eijgendaal, Gerrit Klein, Maria Terhorst-Van Amstel, Klaas Zwier, Nico Bruins, Hendrikus Rigter, Erik Gout
Life of this patent
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Abstract
The invention relates to a stable polymorphic form of the compound 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate (INNM bifeprunox mesylate), a method for the preparation of said polymorphic form and its use in pharmaceutical products, especially in pharmaceutical products for the treatment of psychotic disorders and Parkinson's disease.
Claims22
A pharmaceutical composition comprising an effective amount of a crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, exhibiting an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ at approximately 7.0, 9.3, 10.0, 12.5, 15.4, 16.7, 17.2, 17.4, 17.7, 18.7, 21.3, 22.2, 25.2, 27.2, 28.3, 28.8 and 30.1, and at least one pharmaceutically acceptable excipient.
A pharmaceutical composition comprising an effective amount of a crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, characterized by an X-ray powder diffraction (=XRPD) pattern substantially as shown in FIG. 1, and at least one pharmaceutically acceptable excipient.
A pharmaceutical composition comprising an effective amount of a crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, having a melting point at about 277° C., and at least one pharmaceutically acceptable excipient.
A pharmaceutical composition comprising an effectjve amount of a crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, characterized by a complete DSC trace substantially as shown in FIG. 2, and at least one pharmaceutically acceptable excipient.
A pharmaceutical composition comprising an effective amount of a crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, exhibiting an attenuated total reflectance infrared spectrum having characteristic absorption bands expressed in reciprocal centimeters at approximately 1764, 1217, 795, 746 and 694, and at least one pharmaceutically acceptable excipient.
A pharmaceutical composition comprising an effective amount of a crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, characterized by a complete IR spectrum substantially as shown in FIG. 3, and at least one pharmaceutically acceptable excipient.
A pharmaceutical composition comprising an effective amount of a crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, exhibiting 13C solid state NMR chemical shifts expressed relative to glycine (δc=176.03 for the C═O resonance) at approximately 40.4, 48.7, 56.5, 106.8 and 137.7 ppm, and at least one pharmaceutically acceptable excipient.
A pharmaceutical composition comprising an effective amount of a crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, characterized by a complete 13C solid state NMR chemical substantially as shown in FIG. 4, and at least one pharmaceutically acceptable excipient.
A pharmaceutical composition comprising an effective amount of a crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate exhibiting a single crystal X-ray crystallographic analysis at 150K with (a) crystal parameters that are approximately equal to the following:
- Cell dimensions
- a = 9.283 Å
- b = 10.737 Å
- c = 12.690 Å
- α = 98.553°
- β = 93.749°
- γ = 116.097°
- Crystal system
- triclinic
- Space group
- P-1
- Molecules/unit cell
- 2
- Density (g/cm3)
- 1.481
- and (b) atomic positions of all atoms relative to the origin of the unit cell as recited in Table 5, and at least one pharmaceutically acceptable excipient.
A pharmaceutical composition comprising an effective amount of a crystalline polymorph of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate, characterized by a single X-ray diffraction substantially as shown in FIG. 5 and at least one pharmaceutically acceptable excipient.
A pharmaceutical composition comprising an effective amount of 7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate and a mixture of lactulose monohydrate, microcrystalline lactose, microcrystalline cellulose, sodium starch gylcolate type A and sodium stearyl fumarate.
Dependencies are inferred from the claim text.