Polymorphs
First Claim
Patent Images
1. A method of preparing an anhydrous polymorph A of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine, the method comprising:
- heating polymorph B or a mixture of polymorphs A and B to temperatures>
40°
C.;
whereinsaid anhydrous polymorph A melts at 206±
3°
C., andsaid anhydrous polymorph A exhibits an X-ray powder diagram having characteristic reflections at the following d values;
11.59 Å
, 7.60 Å
, 7.15 Å
, 3.86 Å
, 3.54 Å and
3.47 Å
;
and whereinsaid anhydrous polymorph B transforms reversibly into the polymorph A at temperature of 10-40°
C., andsaid anhydrous polymorph B exhibits an X-ray powder diagram having characteristic reflections at the following d values;
11.3 Å
, 9.36 Å
, 7.48 Å
, 7.0 Å and
3.77 Å
.
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Abstract
The invention relates to polymorphous crystal modifications of a DPP-IV inhibitor, the preparation thereof and the use thereof for preparing a medicament.
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Citations
10 Claims
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1. A method of preparing an anhydrous polymorph A of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine, the method comprising:
-
heating polymorph B or a mixture of polymorphs A and B to temperatures>
40°
C.;
whereinsaid anhydrous polymorph A melts at 206±
3°
C., andsaid anhydrous polymorph A exhibits an X-ray powder diagram having characteristic reflections at the following d values;
11.59 Å
, 7.60 Å
, 7.15 Å
, 3.86 Å
, 3.54 Å and
3.47 Å
;and wherein said anhydrous polymorph B transforms reversibly into the polymorph A at temperature of 10-40°
C., andsaid anhydrous polymorph B exhibits an X-ray powder diagram having characteristic reflections at the following d values;
11.3 Å
, 9.36 Å
, 7.48 Å
, 7.0 Å and
3.77 Å
.- View Dependent Claims (2, 3, 4, 5, 6, 7, 8)
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5. The method according to claim 1 wherein anhydrous polymorph B has an X-ray powder diagram as shown in
FIG. 4 . -
6. The method of claim 1, wherein anhydrous polymorph B is characterized in that the reflection at 11.3 Å
- in the X-ray powder diagram has a relative intensity of 100% and the X-ray powder diagram exhibits no reflections having a relative intensity of 1% or more at the following d values;
11.59 Å
, 7.60 Å
, and 7.15 Å
.
- in the X-ray powder diagram has a relative intensity of 100% and the X-ray powder diagram exhibits no reflections having a relative intensity of 1% or more at the following d values;
-
7. The method according to claim 1, wherein polymorph B is characterised by its lattice metrics:
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8. A method of preparing a medicament, the method comprising
i) preparing the anhydrous polymorph A by the method of claim 1, and ii) combining the anhydrous polymorph A with one or more inert carriers to provide a medicament containing 0.1% to 0.5%, or 0.5% to 1.5%, or 1% to 3% of the anhydrous polymorph A based on the total weight of the polymorph A and the one or more inert carriers.
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9. A method of preparing anhydrous polymorph A or B, or a mixture thereof, of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine, the method comprising crystallizing polymorph A or B, or a mixture thereof, from a solution of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in ethanol,
wherein anhydrous polymorph A is characterised in that it melts at 206± - 3°
C., and further characterised in that it exhibits an X-ray powder diagram having characteristic reflections at the following d values;
11.59 Å
, 7.60 Å
, 7.15 Å
, 3.86 Å
, 3.54 Å and
3.47 Å
,wherein anhydrous polymorph B is characterised in that it transforms reversibly into polymorph A at a temperature of 10-40°
C., and further characterised in that it exhibits an X-ray powder diagram having characteristic reflections at the following d values;
11.3 Å
, 9.36 Å
, 7.48 Å
, 7 Å and
3.77 Å
. - View Dependent Claims (10)
- 3°
Specification