| 摘要 |
A solid oral pharmaceutical composition in the form of tablets including:—a first solid oral pharmaceutical formulation in the form of at least one micro-tablet, the micro-tablet consisting of a core including at least one Krebs cycle precursor salt as active ingredient, and of a coating including at least one coating agent, and—a second oral pharmaceutical formulation in the form of at least one mini-tablet, the mini-tablet consisting of a core including at least one bicarbonate salt as active ingredient and at least one prolonged-release matrix, and of a coating including at least one coating agent. The use thereof as a medicament, in particular in the treatment and/or prevention of cystinuria. |
| 主权项 |
1. A solid pharmaceutical composition for oral use in the form of tablets for treating cystinuria, comprising:
a first solid pharmaceutical formulation for oral use in the form of at least one microtablet, said microtablet being constituted by: a core comprising as active ingredient at least one Krebs cycle precursor salt selected from the group consisting of fumarates, malates, citrates, alpha-ketoglutarate, succinyl-coenzyme A, succinates and oxaloacetate, and a coating comprising at least one pH independent coating agent selected from the group consisting of ethyl cellulose, paraffin waxes, beeswax, carnauba wax, copolymers of ammonium methacrylate of type A and B, and polyacrylates with dispersion of about 30%, wherein the first formulation comprises from 1 to 3% by weight of said at least one coating agent relative to the total weight of the first formulation and has an in vitro dissolution in a dissolution medium buffered at any pH in a range between 1.3 and 7, with a dissolution apparatus of type 2, at a rate from 30 to 50% in 1 hour; and a second solid pharmaceutical formulation for oral use in the form of at least one mini-tablet, said mini-tablet being constituted by: a core comprising as active ingredient at least one bicarbonate salt selected from the group consisting of potassium bicarbonate, sodium bicarbonate and magnesium bicarbonate, and at least one sustained-release hydrophilic matrix selected from the group consisting of sodium salts of carboxymethyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, methyl cellulose, the at least one sustained-release hydrophilic matrix being 10% to 30% by weight of the second-formulation; and a coating comprising from 1% to 20% by weight, relative to the total weight of the second formulation, of at least one pH independent coating agent selected from the group consisting of ethyl cellulose, paraffin waxes, beeswax, carnauba wax, copolymers of ammonium methacrylate of type A and B, and polyacrylates with dispersion of about 30%, wherein the second formulation has an in vitro dissolution in a dissolution medium buffered at any pH in a range between 1.3 and 7, with a dissolution apparatus of type 2, at a rate of 5% to 15% in one hour. |
