| 摘要 |
Means for controlling the formation amount of a formed amide form in relation to a pharmaceutical composition containing luliconazole is provided. Disclosed is a pharmaceutical composition containing 1) luliconazole and 2) one component or two or more components selected from carboxylic acid and derivative thereof, ketone, phosphoric acid and derivative thereof, local anesthetic, antihistamine, and POE-based nonionic surfactant; wherein a content of an amide derivative of luliconazole is not more than 0.2% by mass with respect to a charged amount of luliconazole after storage at 60° C. for 3 weeks or at 40° C. for 6 months. |
| 主权项 |
1. A method for producing a pharmaceutical composition characterized in that
a content of an amide form represented by Chemical Formula (2) is not more than 0.2% by mass with respect to a charged amount of luliconazole after storage at 60° C. for 3 weeks or at 40° C. for 6 months, the method comprising: a step of performing under a severe condition (60° C. for 3 weeks) or an accelerated condition (40° C. for 6 months) as to a formulation candidate containing: 1) luliconazole represented by Chemical Formula (1); and 2-1) a combination of diisopropyl adipate; and one component or two or more components selected from 1,3-butanediol, propylene glycol, and polypropylene glycol, without comprising benzyl alcohol, or N-methyl-2-pyrrolidone; or 2-2) a combination of methyl ethyl ketone; and one component or two or more components selected from 1,3-butanediol, polyethylene glycol, propylene glycol, polypropylene glycol, and N-methyl-2-pyrrolidone; measuring a content of an amide form represented by Chemical Formula (2) by HPLC utilizing a following HPLC condition, and selecting a formulation of which content of an amide form is not more than 0.2% by mass as a pharmaceutical composition; HPLC condition: ODS-2 4.6×150 mm, column temperature: 40° C., mobile phase: 0.15% sodium undecane-1-sulfonate mixture liquid (water/acetonitrile/acetic acid (100) (50:49:1, v/v/v)) solution, flow rate: 1.0 mL/min., detection: 295 nm: |
