Method for solubilizing metronidazole
View Patent ↗Metronidazole is solubilized in an aqueous phase, by mixing same with niacinamide and at least two glycolic cosolvents; the resulting solutions and pharmaceutical compositions comprised thereof are useful for the treatment of dermatological conditions/afflictions, notably rosacea.
1. A process for solubilizing metronidazole, comprising admixing, in an aqueous phase, said metronidazole with niacinamide or salt thereof and at least two glycolic cosolvents, in the absence of cyclodextrin.
2. The solubilization process as defined by claim 1 , wherein the proportion of metronidazole, by mass relative to the total mass of the resulting solution, is greater than or equal to 0.75%.
3. The solubilization process as defined by claim 2 , wherein the proportion of metronidazole, by mass relative to the total mass of the resulting solution, is greater than or equal to 1%.
4. The solubilization process as defined by claim 1 , wherein the niacinamide/metronidazole molar ratio is less than 9.
5. The solubilization process as defined by claim 4 , wherein the niacinamide/metronidazole molar ratio is less than or equal to 5.5.
6. The solubilization process as defined by claim 1 , said glycolic cosolvents comprising propylene glycol and at least one polyethylene glycol.
7. The solubilization process as defined by claim 6 , said at least one polyethylene glycol comprising PEG 400.
8. The solubilization process as defined by claim 1 , wherein two glycolic cosolvents are admixed.
9. The solubilization process as defined by claim 8 , wherein said glycolic cosolvents are present in a ratio by mass of 1:1.
10. The solubilization process as defined by claim 1 , which comprises the following steps:
a) preparing a solution of niacinamide in water, until complete dissolution of the niacinamide is attained,
b) introducing the glycolic cosolvents into the solution obtained in a),
c) homogenizing the solution obtained in b), and then adding a defined amount of metronidazole,
d) after complete dissolution of the metronidazole, filtering the solution obtained.
11. An aqueous solution of metronidazole, prepared according to the process as defined by claim 1 .
12. An aqueous solution comprising metronidazole, niacinamide or salt thereof and at least two glycolic cosolvents.
13. The aqueous solution as defined by claim 12 , devoid of cyclodextrin.
14. The aqueous solution as defined by claim 12 , which comprises:
1) metronidazole in a proportion of greater than or equal to 1%,
2) niacinamide in a proportion such that the niacinamide/metronidazole molar ratio is less than 9,
3) propylene glycol and at least one polyethylene glycol in a ratio by mass of about 1.1.
15. The aqueous solution as defined by claim 14 , wherein the niacinamide/metronidazole molar ratio is less than or equal to 5.5.
16. The aqueous solution as defined by claim 15 , which comprises propylene glycol and polyethylene glycol 400.
17. A pharmaceutical composition which comprises the aqueous solution as defined by claim 12 .
18. A regime or regimen for the treatment of a dermatological condition/affliction, comprising administering to a subject in need of such treatment, a thus effective amount of a pharmaceutical composition as defined by claim 17 .
19. A regime or regimen for the treatment of rosacea, comprising topically applying onto the affected skin area of a subject in need of such treatment, a thus effective amount of a pharmaceutical composition as defined by claim 17 .
20. The regime or regimen as defined by claim 19 , said pharmaceutical composition being devoid of cyclodextrin.
21. The pharmaceutical composition as defined by claim 17 , formulated as a salve, cream, milk, ointment, powder, impregnated pad, syndet, lotion, gel, spray, foam, suspension, stick, shampoo, washing base, microspheres, nanospheres, vesicles, or a controlled release patch.