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 solid dosage form comprising:
a) a roller compacted granulate consisting of:
i) one or more regularly shaped calcium-containing compounds as an active substance,
ii)one or more pharmaceutically acceptable sugar alcohols having a micro structure selected from sorbitol and isomalt, wherein the one or more sugar alcohols have a mean particle size of at the most 150 micrometers, and
iii) mannitol,
wherein the roller compacted granulate has been prepared by roller compaction; and
b) one or more pharmaceutically acceptable excipients, wherein the excipients are combined with the roller compacted granulate after roller compaction.
2. A solid dosage form according to claim 1 for oral administration.
3. A solid dosage form according to claim 1 in the form of a single unit or a multiple unit dosage form.
4. A solid dosage form according to claim 3 in the form of tablets, capsules, sachets, beads, pellets or the like.
5. A solid dosage form according to claim 4 in the form of tablets.
6. A solid dosage form according to claim 5 , wherein the tablets have a shape and dimensions essentially as shown in FIG. 24 herein.
7. A solid dosage form according to claims 1 containing an amount of the one or more calcium-containing compounds corresponding to from about 250 to about 1000 mg calcium.
8. A solid dosage form according to claim 1 , wherein the amount of the one or more calcium-containing compounds corresponds to from about 400 to about 600 mg calcium.
9. A solid dosage form according to claim 1 , wherein the total concentration of the one or more calcium-containing compound in the dosage form is in a range of from about 40% to about 99% w/w.
10. A solid dosage form according to claim 1 , wherein the total concentration of the roller compacted granulate contained in the dosage form is from about 65% to about 100% w/w.
11. A solid dosage form according to claim 1 containing 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.
12. A solid dosage form according to claim 1 containing 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.
13. A solid dosage form according to claim 1 , wherein a SEM photo of a fractured surface of the solid dosage form shows that a surface of a deformed particle of sugar alcohol is in close contact with surfaces of the crystals of the one or more calcium-containing compound.
14. A solid dosage form according to claim 1 in the form of tablets, wherein the crushing strength of the tablets when stored in open petri dishes at 25° C. and 60% RH at the most changes 50% during a time period that starts 5 days after manufacture and runs during the remaining storage period of one month.
15. A solid dosage form according to claim 1 in the form of a chewable, suckable or swallowable tablet.
16. A solid dosage form according to claim 15 , which has an acceptable taste with respect to sweetness, flavour and chalkiness when tested by a professional or skilled sensory test panel of at least 6 persons.
17. A solid dosage form according to claim 1 comprising a sweetener selected from the group consisting of dextrose, fructose, glycerin, glucose, isomalt, lactitol, lactose, maltitol, maltose, mannitol, sorbitol, sucrose, tagatose, trehalose, xylitol, alitame, aspartame, acesulfam potassium, cyclamic acid, cyclamate salt, neohesperidine dihydrochalcone, thaumatin, saccharin, saccharin salt, and mixtures thereof.
18. A solid dosage form according to claim 17 wherein the saccharin salt is selected from the group consisting of ammonium saccharin, calcium saccharin, potassium saccharin, and sodium saccharin.
19. A roller compacted granulate consisting of:
i) one or more regularly shaped calcium-containing compounds as an active substance,
ii)one or more pharmaceutically acceptable sugar alcohols having a micro structure selected from sorbitol and isomalt, wherein the one or more sugar alcohols have a mean particle size of at the most 150 micrometers, and
iii) mannitol.
20. The roller compacted granulate according claim 19 , wherein the one or more calcium-containing compound is in the form of crystals having a specific surface area below 1.5 m 2 /g.
21. The roller compacted granulate according claim 19 , wherein the concentration of the pharmaceutically acceptable sugar alcohol in the roller compacted granulate is at least 5% w/w.
22. The roller compacted granulate according claim 19 , wherein the calcium-containing compound is calcium carbonate.
23. The roller compacted granulate according claim 19 , wherein the content of the calcium-containing compound in the roller compacted granulate is in a range of from about 40% to about 100% w/w.
24. The roller compacted granulate according claim 19 , containing 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.
25. A solid dosage form comprising:
a) a roller compacted granulate consisting of:
i) one or more regularly shaped calcium-containing compounds as an active substance,
ii)one or more pharmaceutically acceptable sugar alcohols having a micro structure selected from sorbitol and isomalt, provided as dry particles, wherein the one or more sugar alcohols have a mean particle size of at the most 150 micrometers, and
iii) mannitol,
wherein the roller compacted granulate has been prepared by roller compaction; and
b) one or more pharmaceutically acceptable excipients, wherein the excipients are combined with the roller compacted granulate after roller compaction.