JP2016534081A5 - Method for preparing an oral dosage form with enhanced oral bioavailability of zoledronic acid - Google Patents

Claims (13)

A method of preparing an oral dosage form having enhanced oral bioavailability of zoledronic acid, comprising:
  Mixing the disodium salt form of zoledronic acid with excipients;
The method results in the disodium salt form of zoledronic acid in the dosage form having enhanced oral bioavailability in mammals compared to the diacid form of zoledronic acid. When the dosage form is administered to the mammal, the dosage form has oral bioavailability resulting in an area under the plasma concentration curve of zoledronic acid from about 4 ng · hr / mL to about 2000 ng · hr / mL. Item 2. The method according to Item 1. When the dosage form is administered to the mammal, the dosage form has oral bioavailability that results in an area under the plasma concentration curve of zoledronic acid from about 100 ng · hr / mL to about 2000 ng · hr / mL. Item 3. The method according to Item 2. When the dosage form is administered to the mammal, the dosage form has oral bioavailability resulting in an area under the plasma concentration curve of zoledronic acid from about 20 ng · hr / mL to about 700 ng · hr / mL. Item 3. The method according to Item 2. The method of claim 2, wherein the dosage form is manufactured as a solid comprising at least about 50% (w / w) zoledronic acid. 3. The method of claim 2, wherein the dosage form is suitable for administration at intervals of about 3 to about 4 weeks. The dosage form is prepared in a form suitable for administration once a week or 3 to 5 times a month;
  When the dosage form is administered to the mammal, the dosage form has oral bioavailability resulting in an area under the plasma concentration curve of zoledronic acid from about 20 ng · hr / mL to about 700 ng · hr / mL. Item 2. The method according to Item 1. The dosage form is prepared in a form suitable for daily administration,
  When the dosage form is administered to the mammal, the dosage form has oral bioavailability resulting in an area under the plasma concentration curve of zoledronic acid from about 4 ng · hr / mL to about 100 ng · hr / mL. Item 2. The method according to Item 1. The method of claim 1, wherein the dosage form is a solid. The method of claim 1, wherein oral bioavailability of the dosage form in the mammal is improved by at least about 20% relative to administration of the diacid form of zoledronic acid. The dosage form comprises an amount of disodium salt form of zoledronic acid, based on moles, to achieve the same plasma concentration of zoledronic acid, less than the possible amount of the diacid form of zoledronic acid. Item 2. The method according to Item 1. The dosage form comprises a disodium salt form that is at least about 10 mol% less than the amount of zoledronic acid in the diacid form that can be administered to achieve the same plasma concentration of zoledronic acid in the mammal. The method according to 1. The dosage form is about 0.8 n based on moles. _d About 1.2n _d An amount of said disodium salt form having a value of
n _d = (B _a / B _d ) (N _a ) And
b _a Is the oral bioavailability of the diacid form, b _d Is the oral bioavailability of the disodium salt form, n _a The method of claim 1, wherein is the number of moles of zoledronic acid in the diacid form that can be administered to achieve the same plasma concentration of zoledronic acid in the mammal.