Particulate comprising a calcium-containing compound and a sugar alcohol
The present invention relates to a particulate material and a solid dosage form notably tablets comprising a regularly shaped calcium-containing compound such as a calcium salt as a therapeutically and/or prophylactically active substance and a pharmaceutically acceptable sugar alcohol such as, e.g., sorbitol and/or isomalt that has a micro structure as evidenced by SEM. The invention also relates to a process for the preparation of the particulate material and solid dosage form. The process involves agglomeration of the calcium-containing compound and the pharmaceutically acceptable sugar alcohol by means of roller compaction. The particulate material obtained by roller compaction is suitable for use in the further processing of the particulate material into e.g. tablets such as chewing tablets.
1. A process for the preparation of a particulate material comprising one or more regularly shaped calcium-containing compounds as an active substance and one or more pharmaceutically acceptable sugar alcohols having a micro structure, the process comprising roller compaction of a composition comprising at least 60% w/w of a regularly shaped calcium-containing compound and one or more pharmaceutically acceptable sugar alcohols having a micro structure; wherein the particulate material is obtained without use of any solvent; the pharmaceutically acceptable sugar alcohol employed has a mean particle size of at the most about 150 μm; the calcium-containing compound is calcium carbonate; and the sugar alcohol is sorbitol or isomalt or mixtures thereof.
2. A process according to claim 1 , wherein the pharmaceutically acceptable sugar alcohol, when compressed into tablets containing 100% w/w of the sugar alcohol, has a slope of correlation between crushing strength, measured in N, and compression pressure, measured in N, of 7×10 −3 or more.
3. A process according to claim 1 , wherein the pharmaceutically acceptable sugar alcohol has binding properties.
4. A process according to claim 1 , wherein the one or more calcium-containing compound is in the form of crystals having a rounded or a cubic shape.
5. A process according to claim 1 , wherein the concentration of the pharmaceutically acceptable sugar alcohol in composition that is subject to roller compaction is at least about 5% w/w.
6. A process according to claim 1 , wherein the pharmaceutically acceptable sugar alcohol employed has a mean particle size of at the most about 110 μm.
7. A process according to claim 1 , wherein the pharmaceutically acceptable sugar alcohol employed has a mean particle size in a range of from about 5 to about 150 μm.
8. A process according to claim 1 , wherein the sugar alcohol is sorbitol.
9. A process according to claim 8 , wherein the mean particle size of sorbitol is in a range of from about 25 to about 50 μm.
10. A process according to claim 1 , wherein the sugar alcohol is isomalt.
11. A process according to claim 10 , wherein the mean particle size of isomalt is in a range of from about 20 to about 50 μm.
12. A process according to claim 1 , wherein the composition that is subjected to roller compaction contains from about 60 to about 95% w/w of the calcium-containing compound and from about 5 to about 40% w/w of the pharmaceutically acceptable sugar alcohol, provided that the sum does not exceed 100% w/w.
13. A process according to claim 1 , wherein the composition that is roller compacted contains from about 60 to about 94% w/w of the calcium-containing compound, from about 5 to about 35% w/w of the pharmaceutically acceptable sugar alcohol and from about 1 to about 15% w/w of one or more pharmaceutically acceptable excipients and/or active substances, provided that the sum of ingredients amounts to 100% w/w.
14. A process according to claim 13 , wherein the composition contains from about 65% to about 80% w/w of the calcium-containing compound and from about 15% to about 25% w/w of sorbitol or isomalt or mixtures thereof.
15. A process according to claim 1 , wherein the pharmaceutically acceptable sugar alcohol employed is lump breaked before admixing it with the calcium-containing compound.
16. A process according to claim 1 , further comprising a step of admixing to the composition that has been subjected to roller compaction one or more pharmaceutically acceptable excipients, additives or active substances.
17. A process according to claim 1 further comprising a step of shaping the particulate material obtained into a solid dosage form.