Patent EA-001213-B1 (EA)
Title: Liquid alendronate formulations
Inventor: NERURKAR MANEESH J
IPC: A61K47/26
Filed: 1997-10-02
Abstract: 1. An aqueous liquid pharmaceutical formulation comprising: alendronic acid or a pharmaceutically acceptable salts as na active ingredient; a sufficient amount of a buffer such that: A) the pH of the formulation is between approximately 3.5 and approximately 7.5; and B) 15 ml of the formulation is able to raise the pH of 50 ml 0.1N HCl to a pH of at least 3; and optionally, one or more additional agents selected from the group consisting of preservatives, flavoring agents, colorants, and sweeteners. 2. A formulation according to claim 1, wherein the buffer is a critic acid/sodium citrate or a tartaric acid/sodium tartrate buffer system. 3. A formulation according to claim 2 wherein the concentration of alendronate monosodium trihydrate is 0.1-0.9 mg/ml on an alendronic acid basis. 4. A formulation according to claim 3 wherein the concentration of alendronate monosodium trihydrate is 0.133 or 0.67 mg/ml on an alendronic acid basis. 5. A formulation according to claim 2, wherein the concentration of citric acid and sodium citrate present is 0.06-0.65 M, the pH of the formulation is 3.5-7.5, and the pH of 50 ml of 0.1N HCl when 15 ml of the formulation is added is above pH 3. 6. An aqueous liquid pharmaceutical formulation comprising (in mg/ml): alendronate monosodium trihydrate (on an alendronic acid basis) 	0.2-0.9 sodium benzoate 	1.0-2.0 sodium citrate dehydrate 	75-125 citric acid anhydrous 	0.3-40 xylitol 	100-640 wherein the citric acid and sodium citrate present in the invention is 0.06-0.65M, the pH of the formulation is 3.5-7.5 and the pH of 50 ml of 0.1N HCl when 15 ml of the formulation is added is above pH 3.  7. A liquid pharmaceutical formulation according to claim 6 comprising (in mg/ml): alendronate monosodium trihydrate (on an alendronic acid basis) 	0.1-0.9 sodium benzoate 	1.0-2.0 potassium sorbate 	1.0-2.0 xylitol 	400 artificial flavoring 	5-50 sodium citrate dehydrate 	75-125 citric acid, anhydrous 	0.3-40  8. A pharmaceutical formulation according to claim 6 wherein the alendronate monosodium trihydrate is present at 0.33 to 0.67 mg/ml on an alendronic acid basis. 9. An aqueous liquid pharmaceutical formulation comprising (in mg/ml): alendronate monosodium trihydrate (on an alendronic acid basis)	0.1-0.9 tartaric acid, NF	70-140 sodium hydroxide pellets, NF	36-72 xylitol 	100-640 sodium benzoate NF	0-3 flavor N & A #782 Orange	0-100  10. A pharmaceutical formulation according to claim 9 wherein the alendronate monosodium trihydrate is present at a concentration of 0.13 to 0.67 mg/ml on an alendronic acid basis. 11. A pharmaceutical formulation according to claim 2 wherein the sum total amount of citric acid and sodium citrate present in the formulation is at least about 50 mg/ml. 12. A pharmaceutical formulation according to claim 8 wherein the sum total amount of citric acid and sodium citrate present in the formulation is at least about 75 mg/ml. 13. A pharmaceutical formulation according to claim 8 wherein the sum total amount of citric acid and sodium citrate present in the formulation is at least about 100 mg/ml. 14. A method of inhibiting bone resorption comprising administering an aqueous liquid formulation of alendronic acid or pharmaceutically acceptable salt and a buffer so that the alendronic acid is not exposed to a gastro-intestinal environment which has a pH below about 3.5. 15. An aqueous liquid pharmaceutical formulation prior to mixing comprising: alendronic acid or a pharmaceutically acceptable salt as an active ingredient; a sufficient amount of a buffer such that: A) the pH of the formulation is between approximately 3.5 and approximately 7.5; and B) 15 ml of the formulation is able to raise the pH of 50 ml 0.1N HCl to a pH of at least 3; and  optionally, one or more additional agents selected from the group consisting of preservatives, flavoring agents, colorants, and sweeteners. 16. An aqueous liquid pharmaceutical formulation prepared by combining: alendronic acid or a pharmaceutically acceptable salt as an active ingredient; a sufficient amount of a buffer such that: A) the pH of the formulation is between approximately 3.5 and approximately 7.5; and  B) 15 ml of the formulation is able to raise the pH of 50 ml 0.1N HCl to a pH of at least 3; and  optionally, one or more additional agents selected from the group consisting of preservatives, flavoring agents, colorants, and sweeteners. 17. A method of preparing an aqueous liquid pharmaceutical composition comprising the step of combining alendronic acid or a pharmaceutically acceptable salt as an active ingredient; a sufficient amount of a buffer such that: A) the pH of the formulation is between approximately 3.5 and approximately 7.5; and B) 15 ml of the formulation is able to raise the pH of 50 m1 0.1N HCl to a pH of at least 3; and  optionally, one or more additional agents selected from the group consisting of preservatives, flavoring agents, colorants, and sweeteners.