Disintegrable formulations of lanthanum carbonate
View Patent ↗Disintegrable preparations of lanthanum carbonate prepared by co-precipitation, facilitating the manufacture of oral pharmaceutical dosage forms such as tablets, capsules, powders, granules, and sprinkles, and the use of such dosage forms to treat subjects with hyperphosphatemia are disclosed.
1. A rapidly disintegrable pharmaceutical dosage form comprising co-precipitated lanthanum carbonate, wherein said lanthanum carbonate is prepared by coprecipitation with an excipient and an optional disintegrant, wherein the excipient is selected from the group consisting of a saccharide, a pentahydric alcohol, a hexahydric alcohol and a mixture thereof;
said coprecipitation comprising freezing an aqueous mixture comprising said lanthanum carbonate, said excipient and said optional disintegrant to produce a frozen mixture; and
lyophilizing said frozen mixture under vacuum.
2. The pharmaceutical dosage form of claim 1 wherein the excipient is present in a 1:1 ratio with the lanthanum carbonate.
3. The pharmaceutical dosage form of claim 1 , comprising 100 to 1000 mg of the lanthanum carbonate, 100 to 750 mg of the excipient and 0-25 wt. % of the disintegrant, based on the weight of the lanthanum carbonate.
4. The pharmaceutical dosage form of claim 1 wherein the disintegrant is selected from the group consisting of colloidal silicon dioxide, silicon dioxide, starch, and povidone.
5. The pharmaceutical dosage form of claim 1 , wherein the lanthanum carbonate is hydrated and has the general formula: La 2 (CO 3 ) 3 .xH 2 O, wherein x has a value of 4-15.
6. The pharmaceutical dosage form of claim 1 , wherein a ratio of the lanthanum carbonate to the excipient to the disintegrant is 25-75: 25-75: 2-25.
7. The pharmaceutical dosage form of claim 6 , wherein the ratio is 40-50:40-50:10-20.
8. The pharmaceutical dosage form of claim 1 , said dosage form being compressed into an oral solid form.
9. The pharmaceutical dosage form of claim 8 , wherein the oral solid form is adapted to be dissolved into a liquid form prior to ingestion by the patient.
10. The pharmaceutical dosage form of claim 9 , wherein the dosage form disintegrates in between 2 and 20 minutes.
11. The pharmaceutical dosage form of claim 9 , wherein the dosage form has a phosphate binding capacity of between 2.5 and 5 mmol/g.
12. A method of treating hyperphosphataemia with the pharmaceutical dosage form of claim 1 .
13. A method of treating hyperphosphataemia according to claim 12 , wherein the dosage form is a tablet which is adapted to be dissolved in a liquid prior to administration.
14. A pharmaceutical dosage form comprising a product prepared by lyophilization of a mixture of La 2 (CO 3 ) 3 , Mannitol, and colloidal SiO 2 in a ratio of 1-75:1-75:0-34;
wherein the lanthanum carbonate is hydrated to a water content of between about 6-11 moles of water, and the dosage form has a disintegration time of from about 195 to 400 seconds and a phosphate binding capacity of between about 3.4 and about 4.6 mmol/g.
15. The dosage form of claim 14 , wherein the ratio is 5:3-5:0-2.
16. A process for preparing a rapidly disintegrating pharmaceutical dosage form comprising co-precipitating lanthanum carbonate hydrate with an excipient and an optional disintegrant by lyophilization,
wherein the excipient is selected from the group consisting of a saccharide, a pentahydric alcohol, a hexahydric alcohol, and a mixture thereof,
wherein said coprecipitation comprises freezing an aqueous mixture comprising said lanthanum carbonate, said excipient and said optional disintegrant to produce a frozen mixture; and
lyophilizing said frozen mixture under vacuum.
17. The process of claim 16 , wherein 100 to 1000 mg of the lanthanum carbonate hydrate is coprecipitated with 100 to 1000 mg of the excipient and 0-25 wt. % of the disintegrant, based on the weight of the lanthanum carbonate.
18. The process of claim 16 , wherein the disintegrant is selected from the group consisting of colloidal silicon dioxide, silicon dioxide, starch, and povidone.
19. The process of claim 16 wherein the hydrated lanthanum carbonate has the general formula: La 3 (CO 3 ) 3 .xH 2 O, wherein x has a value of 4-15.
20. The method of claim 16 wherein a ratio of the lanthanum carbonate to the excipient is 1:1.
21. The process of claim 16 wherein the composition is compressed into an oral solid form following coprecipitation.
22. A rapidly disintegrable pharmaceutical dosage form comprising coprecipitated lanthanum carbonate, wherein said lanthanum carbonate is prepared by coprecipitation with an excipient and an optional disintegrant;
wherein said coprecipitation consists of spray-drying an aqueous mixture consisting of said lanthanum carbonate, said excipient and said optional disintegrant;
said excipient being selected from the group consisting of pentahydric alcohols, hexahydric alcohols, lactose, and mixtures thereof; and
said disintegrant being selected from the group consisting of colloidal silicon dioxide, silicon dioxide, calcium silicate, sodium starch glycolate, sodium carboxymethyl starch, carboxymethyl cellulose, povidone, and mixtures thereof.
23. A process for preparing a rapidly disintegrable pharmaceutical dosage form according to claim 22 , said method comprising:
spray-drying said aqueous mixture consisting of said lanthanum carbonate, said excipient and said optional disintegrant.