Compositions for Oral Administration of Zoledronic Acid or Related Compounds for Treating Disease
Oral dosage forms of bisphosphonate compounds, such as zoledronic acid, can be used to treat or alleviate pain or related conditions. The oral bioavailabilty of zoledronic acid can be enhanced by administering the zoledronic acid in the disodium salt form
1 - 180 . (canceled)
181 . An oral dosage form comprising zoledronic acid in the disodium salt form, wherein the bioavailability, in a mammal, of zoledronic acid in the disodium salt form is greater than the bioavailability of zoledronic acid in the diacid form would be in the same dosage form.
182 . The oral dosage form of claim 181 , wherein the dosage form contains an amount of zoledronic acid in the disodium salt form that provides an area under the plasma concentration curve of zoledronic acid of about 100 ng·h/mL to about 2000 ng·h/mL to a human being to which the dosage form is administered.
183 . The oral dosage form of claim 181 , wherein the dosage form contains an amount of zoledronic acid in the disodium salt form that provides an area under the plasma concentration curve of zoledronic acid of about 20 ng·h/mL to about 700 ng·h/mL to a human being to which the dosage form is administered.
184 . The oral dosage form of claim 181 , wherein the dosage form contains an amount of zoledronic acid in the disodium salt form that provides an area under the plasma concentration curve of zoledronic acid of about 4 ng·h/mL to about 100 ng·h/mL to a human being to which the dosage form is administered.
185 . The oral dosage form of claim 181 , wherein the disodium salt form is present in a lower molar amount than would be present if the zoledronic acid were in the diacid form; and wherein the zoledronic acid in the disodium salt form has an improved bioavailability as compared to the zoledronic acid in the diacid form to the extent that the lower molar amount of the disodium salt in the dosage form does not reduce the amount of zoledronic acid delivered to the plasma of a mammal.
186 . The oral dosage form of claim 185 , containing at least about 20 mole % less of the disodium salt form as compared to the amount of the zoledronic acid in the diacid form that would be present if the zoledronic acid were in the diacid form.
187 . The oral dosage form of claim 185 , wherein the disodium salt form is present in an amount, on a molar basis, that has a value of about 0.9n d to about 1.1 n d , wherein:
n d =( b a /b d )( n a )
wherein b a is the bioavailability of the diacid form, b d is the bioavailability of the disodium salt form, and n a is the number of moles of the diacid form that would be present if the zoledronic acid were in the diacid form.
188 . The oral dosage form of claim 187 , wherein the disodium salt is administered in an amount that has a value of about n d .
189 . The oral dosage form of claim 181 , wherein the dosage form is a solid.
190 . The oral dosage form of claim 181 , wherein the bioavailability of zoledronic acid in the disodium salt form is improved by at least about 10% as compared to an otherwise identical dosage form containing zoledronic acid in the diacid form.
191 - 194 . (canceled)
195 . The oral dosage form of claim 181 , wherein the zoledronic acid in the oral dosage form has a 24 hour sustained plasma level factor of about 1 or higher.
196 . The oral dosage form of claim 181 , wherein the zoledronic acid in the oral dosage form has a 24 hour sustained plasma level factor that is higher than that of intravenously administered zoledronic acid.