Crystalline amoxicillin trihydrate powder
The invention relates to crystalline amoxicillin trihydrate powder having a bulk density higher than 0.45 g/ml. The invention also relates to a process for preparing crystalline amoxicillin trihydrate powder, said process comprising: crystallizing amoxicillin trihydrate from a solution containing dissolved amoxicillin; separating the crystals from said solution; and drying the separated crystals, resulting in crystalline powder having a bulk density higher than 0.45 g/ml.
1. Crystalline amoxicillin trihydrate powder having a bulk density higher than 0.45 g/ml and a d 50 lower than 100 μm.
2. Crystalline powder according to claim 1 , having a tapped density higher than 0.6 g/ml, wherein said tapped density is determined according to USP 24, method II.
3. Crystalline powder according to claim 1 or claim 2 , having a d 50 higher than 10 μm.
4. Crystalline powder according to claim 1 , having a d 10 higher than 3 μm.
5. Crystalline powder according to claim 1 , having a T 85% <55 minutes, wherein T 85% is the period required to effect dissolution of 85 wt. % of a predetermined quantity (500 mg on an anhydrous basis) of the amoxicillin trihydrate in 900 ml water of 37° C.
6. Mixture comprising
(i) crystalline powder according to claim 1 ; and
(ii) (a) granules comprising amoxicillin trihydrate; and/or
(b) a second pharmaceutically active agent; and/or
(c) auxiliaries,
wherein said granules have a d 50 of between 100 and 1000 μm.
7. Product of amoxicillin trihydrate having
(i) T 85% <55 minutes,
(ii) bulk density higher than 0.45 g/ml; and
(iii) a d 50 lower than 100 μm
wherein T 85% is the period required to effect dissolution of 85 wt. % of a predetermined quantity (500 mg on an anhydrous basis) of the amoxicillin trihydrate in 900 ml water of 37° C.
8. Product according to claim 7 , comprising (i) amoxicillin trihydrate powder and (ii) granules comprising amoxicillin, wherein said granules have a d 50 of between 100 and 1000 μm.
9. A composition comprising (i) amoxicillin trihydrate powder and (ii) granules comprising amoxicillin, wherein said amoxicillin trihydrate powder is crystalline amoxicillin trihydrate powder according to claim 1 , wherein said amoxicillin trihydrate power has
(i) T 85% <55 minutes;
(ii) bulk density higher than 0.45 g/ml; and
(iii) a d 50 lower than 100 μm
wherein T 85% is the period required to effect dissolution of 85 wt. % of a predetermined quantity (500 mg on an anhydrous basis) of the amoxicillin trihydrate in 900 ml water of 37° C.; and
wherein said granules have a d 50 of between 100 and 1000 μm.
10. Product according to claim 8 , wherein said granules are free of auxiliaries.
11. Product according to claim 7 , wherein said product is free of auxiliaries.
12. Mixture comprising
(i) product according to claim 7 and
(ii) auxiliaries and/or a second pharmaceutical active agent.
13. Mixture according to claim 12 , said mixture having:
(i) T 85% <60 minutes; and
(ii) bulk density higher than 0.45 g/ml.
14. Mixture according to claim 6 , wherein said second pharmaceutical active agent is clavulanic acid in the form of a salt.
15. Mixture according to claim 6 , wherein said granules are free of auxiliaries, and wherein said granules have a d 50 of between 100 and 1000 μm.
16. A method of preparing a capsule or a tablet comprising filling a capsule or forming a tablet with a material comprising a crystalline powder according to claim 1 .
17. A method of preparing a capsule or a tablet comprising filling a capsule or forming a tablet with a material comprising a mixture according to claim 6 .
18. A method of preparing a capsule or a tablet comprising filling a capsule or forming a tablet with a material comprising a product according to claim 7 .
19. A method of preparing a capsule or a tablet comprising filling a capsule or forming a tablet with a material comprising a mixture according to claim 12 .
20. A capsule comprising a crystalline powder according to claim 1 .
21. A capsule comprising a mixture according to claim 6 .
22. A capsule comprising a product according to claim 7 .
23. A capsule comprising a mixture according to claim 12 .
24. A process for producing a compressed product comprising compressing a crystalline powder according to claim 1 .
25. A process for producing a compressed product comprising compressing a mixture according to claim 6 .
26. A process for producing a compressed product comprising compressing a product according to claim 7 .
27. A process for producing a compressed product comprising compressing a mixture according to claim 12 .
28. Granules or tablets comprising a crystalline powder according to claim 1 , wherein said granules have a d 50 of between 100 and 1000 μm.
29. Granules or tablets comprising a mixture according to claim 6 .
30. Granules or tablets comprising a product according to claim 7 , wherein said granules have a d 50 of between 100 and 1000 μm.
31. Granules or tablets comprising a mixture according to claim 12 , wherein said granules have a d 50 of between 100 and 1000 μm.
32. A process for preparing a pharmaceutical composition comprising forming the composition with a material comprising a crystalline powder according to claim 1 .
33. A process for preparing a pharmaceutical composition comprising forming the composition with a material comprising a mixture according to claim 6 .
34. A process for preparing a pharmaceutical composition comprising forming the composition with a material comprising a product according to claim 7 .
35. A process for preparing a pharmaceutical composition comprising forming the composition with a material comprising a mixture according to claim 12 .