Effervescent compositions comprising bisphosphonates and methods related thereto
The invention provides effervescent composition comprising a bisphosphonate, an acidic compound, an alkaline effervescing component, and optionally an anti-ulcer agent and methods of treating osteoporosis in a mammal using the effervescent compositions.
1 . An effervescent composition comprising:
(a) a bisphosphonate,
(b) an acid component, and
(c) an alkaline effervescing component,
wherein the composition when dissolved in water produces a solution having a buffered pH of about 3 to about 6.5.
2 . The effervescent composition of claim 1 , further comprising an anti-ulcer agent.
3 . The composition of claim 2 , wherein the anti-ulcer agent is an H 2 -antagonist.
4 . The composition of claim 3 , wherein the H 2 -antagonist is selected from the group consisting of ranitidine, cimetidine, famotidine, nizatidine, and combinations thereof.
5 . The composition of claim 2 , wherein the anti-ulcer agent is a proton pump inhibitor.
6 . The composition of claim 5 , wherein the proton pump inhibitor is selected from the group consisting of omeprazole, pantoprazole, lansoprazole, rabeprazole, and combinations thereof.
7 . The composition of claim 2 , wherein the anti-ulcer agent comprises at least one H 2 -antagonist and at least one proton pump inhibitor.
8 . The composition of claim 1 , wherein the bisphosphonate is selected from the group consisting of etidronate, risedronate, ibandronate, alendronate, and combinations thereof.
9 . The composition of claim 1 , wherein the bisphosphonate is etidronate.
10 . The composition of claim 1 , wherein the bisphosphonate is alendronate.
11 . The composition of claim 1 , wherein the bisphosphonate is ibandronate.
12 . The composition of claim 1 , wherein the bisphosphonate is residronate.
13 . The composition of claim 1 , wherein the dissolved buffered solution is capable of mediating the pH of a patient's stomach for at least about 15 minutes or more.
14 . The composition of claim 1 , wherein the acid component comprises citric acid.
15 . The composition of claim 1 , wherein the alkaline effervescing component comprises a carbonate salt and a bicarbonate salt.
16 . The composition of claim 1 , wherein the acid component and the alkaline effervescing component are at least partially reacted with each other during granulation with the bisphosphonate.
17 . The composition of claim 1 , further comprising a sweetener or flavorant.
18 . The composition of claim 1 , further comprising a solubilizing agent.
19 . The composition of claim 18 , wherein the solubilizing agent is selected from the group consisting of polyvinylpyrrolidones, polyethylene glycols, dextrans, and combinations thereof.
20 . The composition of claim 1 , wherein the acid component comprises a non-zero amount of acid equivalents and the solution comprises an amount of a fully deprotonated salt of the acid component that is at least about 1.5 times the amount of acid equivalents.
21 . An effervescent composition comprising:
(a) a bisphosphonate,
(b) an anti-ulcer agent,
(c) an acid component,
(d) an alkaline effervescing component, and, optionally, one or more of the following ingredients selected from:
(e) a sweetener,
(f) a flavorant, and
(g) a solubilizing agent.
22 . The effervescent composition of claim 21 , wherein the acid component and the alkaline effervescing component are at least partially reacted with each other during granulation with the bisphosphonate and/or the anti-ulcer agent.
23 . The composition of claim 21 , wherein the effervescent composition comprises:
(a) about 0.1% to about 19% bisphosphonate,
(b) about 0.5% to about 50% anti-ulcer agent,
(c) about 15% to about 60% acid component
(d) about 20% to about 70% alkaline effervescing component,
(e) about 0% to about 5% sweetener,
(f) about 0% to about 10% flavorant, and
(g) about 0% to about 10% solubilizing agent,
wherein the percent amounts are based on the total weight of the composition.
24 . The composition of claim 23 , wherein the bisphosphonate is etidronate.
25 . An effervescent composition comprising:
(a) a microencapsulated bisphosphonate,
(b) an acid component,
(c) an alkaline effervescing component, and optionally
(d) an anti-ulcer agent.
26 . The effervescent composition of claim 25 , wherein the bisphosphonate is microencapsulated in a cellulosic, gum, or wax coating.
27 . A method of treating osteoporosis in a mammal comprising:
(a) combining an osteoporosis-treating effective amount of the composition of claim 1 with water to form at least a partial solution; and
(b) administering the solution to the mammal orally.
28 . The method of claim 27 , wherein administration of the solution to the mammal produces a stomach pH of at least about 3 or greater in the mammal.
29 . The method of claim 27 , wherein the composition is administered daily, weekly, twice weekly, thrice weekly, biweekly, monthly, or every other month.
30 . The method of claim 27 , wherein the bisphosphonate is alendronate, and the amount of the alendronate to be administered weekly is about 10 mg to about 15 mg.
31 . The method of claim 27 , wherein the bisphosphonate is alendronate, and the amount of the alendronate to be administered monthly is about 50 mg to about 120 mg.
32 . The method of claim 27 , wherein the bisphosphonate is alendronate, and the amount of the alendronate to be administered every other month is about 100 mg to about 300 mg.
33 . A method of inhibiting bone resorption in a mammal comprising:
(a) combining a bone resorption inhibiting amount of the composition of claim 1 with water to form at least a partial solution, and
(b) administering the solution to the mammal orally.
34 . The method of claim 33 , wherein administration of the solution to the mammal produces a stomach pH of at least about 3 or greater in the mammal.
35 . A method of treating osteoporosis in a mammal comprising:
(a) combining an osteoporosis-treating effective amount of the composition of claim 21 with water to form at least a partial solution; and
(b) administering the solution to the mammal orally.
36 . The method of claim 35 , wherein administration of the solution to the mammal produces a stomach pH of at least about 3 or greater in the mammal.
37 . A method of inhibiting bone resorption in a mammal comprising:
(a) combining a bone resorption inhibiting amount of the composition of claim 21 with water to form at least a partial solution, and
(b) administering the solution to the mammal orally.
38 . The method of claim 37 , wherein administration of the solution to the mammal produces a stomach pH of at least about 3 or greater in the mammal.
39 . A method of treating osteoporosis in a mammal comprising:
(a) combining an osteoporosis-treating effective amount of the composition of claim 25 with water to form at least a partial solution; and
(b) administering the solution to the mammal orally.
40 . The method of claim 39 , wherein administration of the solution to the mammal produces a stomach pH of at least about 3 or greater in the mammal.
41 . A method of inhibiting bone resorption in a mammal comprising:
(a) combining a bone resorption inhibiting amount of the composition of claim 25 with water to form at least a partial solution, and
(b) administering the solution to the mammal orally.
42 . The method of claim 41 , wherein administration of the solution to the mammal produces a stomach pH of at least about 3 or greater in the mammal.