Pharmaceutical compositions and salts of a 1,2,4-oxadiazole benzoic acid
Provided herein are pharmaceutical compositions, which comprise a 1,2,4-oxadiazole benzoic acid or a pharmaceutically acceptable salt thereof. Further provided herein are certain pharmaceutically acceptable salts of a 1,2,4-oxadiazole benzoic acid and methods for making the same. Further provided herein are methods of treating or preventing a disease associated with a nonsense mutation or a premature stop codon, comprising administering such pharmaceutical compositions or pharmaceutically acceptable salts to a patient having a disease associated with a nonsense mutation or a premature stop codon.
1. A pharmaceutical composition for ophthalmic administration comprising:
a) a crystalline salt form comprising 3-[5-(2-fluoro-phenyl)-[1,2,4]oxadiazol-3-yl]benzoic acid and a salt selected from the group consisting of a magnesium salt, a potassium salt, a sodium salt, a tromethamine salt, an L-lysine salt, an L-arginine salt and an L-histidine salt; and
b) an isotonizing agent selected from the group consisting of sodium chloride, boric acid, mannitol, sorbitol, trehalose, and glycerin;
wherein the composition has a pH of between about 3 and about 8; and
wherein said salt form is a crystalline salt form that comprises a magnesium salt and has an X-ray powder diffraction pattern substantially as shown in FIG. 2 ;
said salt form is a crystalline salt form that comprises a potassium salt and has an X-ray powder diffraction pattern substantially as shown in FIG. 4 ;
said salt form is a crystalline salt form that comprises a sodium salt and has an X-ray powder diffraction pattern substantially as shown in FIG. 6 ;
said salt form is a crystalline salt form that comprises a tromethamine salt and has an X-ray powder diffraction pattern substantially as shown in FIG. 8 ;
said salt form is a crystalline salt form that comprises an L-lysine salt and has an X-ray powder diffraction pattern substantially as shown in FIG. 12 ;
said salt form is a crystalline salt form that comprises an L-arginine salt and has an X-ray powder diffraction pattern substantially as shown in FIG. 14 ; or
said salt form is a crystalline salt form that comprises an L-histidine salt and has an X-ray powder diffraction pattern substantially as shown in FIG. 16 .
2. The composition of claim 1 further comprising a preservative selected from the group consisting of benzalkonium chloride, benzethonium chloride, disodium ethylenediaminetetraacetic acid, polyquaternium-1, polyhexamethylene biguanide, and chlorobutanol.
3. The composition of claim 1 further comprising a buffer agent selected from the group consisting of sodium monohydrogen phosphate, sodium dihydrogen phosphate, sodium borate, sodium acetate, and sodium citrate.
4. The composition of claim 1 further comprising a wetting polymer selected from the group consisting of sodium polyacrylate, carboxyvinyl polymer, and crosslinked polyacrylate.
5. The composition of claim 1 further comprising a viscosity enhancer selected from the group consisting of carboxymethyl cellulose, carboxymethyl cellulose sodium, methylcellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, polyethylene glycol 300, polyethylene glycol 400, polyvinyl alcohol, povidone, alginates, xanthan gum, gelatin, acacia, tragacanth, dextran 70, gelatin, polysorbate 80, and propylene glycol.
6. The composition of claim 1 further comprising a cyclodextrin selected from the group consisting of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, hydroxypropyl-β-cyclodextrin, hydroxypropyl-γ-cyclodextrin, dimethyl-β-cyclodextrin and dimethyl-γ-cyclodextrin.
7. A method for treating, preventing or managing an ocular disease associated with a nonsense mutation or a premature stop codon in a patient having an ocular disease associated with a nonsense mutation or premature stop codon, comprising administering a pharmaceutical composition of claim 1 to said patient.