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