Effervescent bisphosphonate formulation

• US 20060034921A1
• Filed: 10/19/2005
• Published: 02/16/2006
• Est. Priority Date: 01/05/2004
• Status: Abandoned Application

• Current Assignee: Ashok V. Katdare, Colin R. Gardner, Kenneth A. Kramer
• Original Assignee: Ashok V. Katdare, Colin R. Gardner, Kenneth A. Kramer
• Inventors: Katdare, Ashok V., Kramer, Kenneth A., Gardner, Colin R.
• Application Number:
  US11/253,392
• Publication Number:
  US 20060034921A1
• Time in Patent Office: Days
• US Class Current: 424/466
• CPC Class Codes: A61K 31/663 Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets

Abstract

An effervescent formulation of alendronate contains an acid source, a carbonate source, a binder, a lubricant and optionally, flavoring agents, colorants and sweeteners.

Claims

1. An effervescent pharmaceutical formulation comprising as an active ingredient a bisphosphonate selected from the groups consisting of:

alendronate, cimadronate, clodronate, EB-1053, etidronate, ibandronate, neridronate, olpadronate, pamidronate, risedronate, tiludronate, YH 529, zoledronate, pharmaceutically acceptable salts and esters of the foregoing, and mixtures of the foregoing; and

an acid source selected from the group consisting of;

citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid;

an anhydride of said acids;

an acid salt selected from the group consisting of sodium dihydrogen phosphate, disodium dihydrogen pyrophosphate and sodium acid sulfite; and

mixtures of the acids, anhydrides and acid salts;

a carbonate source selected from the group consisting of;

sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, sodium sesquicarbonate, sodium glycine carbonate, and mixtures thereof;

a binder selected from the group consisting of a non-reducing sugar, polyvinyl pyrrolidone, sodium chloride, sodium benzoate and sodium sulfate;

a lubricant selected from the group consist of stearic acid salts, powdered sodium benzoate, L-leucine, sodium laurel sulfate and PEG; and

optionally, one or more additional agents selected from the group consisting of flavoring agents, colorants, and sweeteners.

2. An effervescent pharmaceutical formulation according to claim 1 wherein the active ingredient comprises alendronate or a pharmaceutically acceptable salt thereof as an active ingredient and further comprising:

an acid source selected from the group consisting of;

citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid;

an anhydride of said acids;

an acid salt selected from the group consisting of sodium dihydrogen phosphate, disodium dihydrogen pyrophosphate and sodium acid sulfite; and

mixtures of the acids, anhydrides and acid salts;

a carbonate source selected from the group consisting of;

sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, sodium sesquicarbonate, sodium glycine carbonate, and mixtures thereof;

wherein the acid source is present in an equal or excess amount compared to the carbonate source, based on molecular equivalent amounts;

a binder selected from the group consisting of mannitol, sorbitol, polyvinyl pyrrolidone, lactose, sodium chloride, sodium benzoate and sodium sulfate;

a lubricant selected from the group consist of stearic acid salts, powdered sodium benzoate, L-leucine, sodium laurel sulfate and PEG; and

optionally, one or more additional agents selected from the group consisting of flavoring agents, colorants, and sweeteners.

3. A formulation according to claim 2 wherein the amount of alendronate or salt thereof is from 1-80 mg.

4. A formulation according to claim 3 wherein the acid source is citric acid, tartaric acid or mixtures thereof.

5. A formulation according to claim 3 wherein the carbonate source is sodium bicarbonate, sodium carbonate, and mixtures thereof.

6. A formulation according to claim 5 wherein the mole ratio of citric acid to bicarbonate is from 1:

1 to 1;

3.

7. A formulation according to claim 5 wherein the binder is mannitol, lactose, dextrose or sorbitol.

8. A formulation comprising (in mg):

Alendronate sodium 5-10 mg (in mg alendronic acid) citric acid 600-750 sodium bicarbonate 300-500 sodium carbonate 20-60 sodium benzoate 5-15 water 0-5.

9. A formulation according to claim 8, further comprising a flavoring agent or a colorant.

10. A formulation comprising (in mg):

Alendronate sodium  

5-10 (in mg alendronic acid) citric acid 450-650 sodium bicarbonate (total)  

 

800-1150.

11. A formulation comprising (in mg):

Alendronate sodium 2.5-10 

(in mg alendronic acid) citric acid 400-800 sodium bicarbonate 1000-2000 sodium carbonate 20-80 sodium benzoate  

25-175 xylitol  

100-300.

12. A formulation made by the process of combining:

Alendronate sodium 2.5-10 

(in mg alendronic acid) citric acid 400-800 sodium bicarbonate 1000-2000 sodium carbonate 20-80 sodium benzoate  

25-175 xylitol  

100-300.