Pharmaceutical composition, method for stabilizing pharmaceutical composition, and method for evaluating storage stability of pharmaceutical composition

A pharmaceutical composition comprising components (A), (b1), (b2), (F), and (G),

• wherein:
• the content of component (A) is 0.01 to 5 weight %,
• the content of component (b1) is 0.1 to 10 times as much by weight as that of the component (A),
• the content of component (b2) is 0.1 to 10 times as much by weight as that of the component (A),
• the content of component (F) is 0.1 to 10 times as much by weight as the total amount of the component (A), the component (b1), and the component (b2),
• the content of component (G) is 0.01 to 2.0 weight % as benzoic acid, and
• the weight ratio of the component (b2) to the component (G) [component (b2)/component (G)] is from 1/5 to 10/1,
• wherein the components (A), (b1), (b2), (F), and (G) are as follows:
• Component (A):
• l-menthol;
• Component (b1):
• a medium-chain fatty acid triacylglycerol;
• Component (b2):
• a medium-chain fatty acid and/or a salt thereof,
• Component (F):
• at least one selected from the group consisting of:
• a sucrose fatty acid ester;
• a polyoxyethylene hydrogenated castor oil;
• and
• a polysorbate;
• and
• Component (G):
• at least one selected from the group consisting of:
• benzoic acid;
• p-hydroxybenzoic acid;
• and
• a salt or an alkyl ester thereof.

A pharmaceutical composition having a cloud point of 30° C. to 75° C. and comprising components (A), (B), (C), (D) and (E) as follows:

• Component (A):
• l-menthol;
• Component (B):
• at least one selected from the group consisting of:
• a medium-chain fatty acid triacylglycerol;
• a medium-chain fatty acid;
• and
• a salt of a medium-chain fatty acid;
• Component (C):
• a nonionic surfactant having a hydrophile-lipophile balance (HLB) of not less than 10;
• Component (D):
• a polyhydric alcohol having not less than three hydroxy groups per molecule and/or a poly(oxyalkylene) glycol;
• and
• Component (E):
• water.

A method for stabilizing a pharmaceutical composition which comprises:

• l-menthol;
• at least one selected from the group consisting of:
• a medium-chain fatty acid triacylglycerol;
• a medium-chain fatty acid;
• and
• a salt of medium-chain fatty acid;
• a nonionic surfactant having a hydrophile-lipophile balance (HLB) of not less than 10;
• and
• water,
• the method comprising:
• combining the pharmaceutical composition with a polyhydric alcohol having not less than three hydroxy groups per molecule and/or a poly(oxyalkylene) glycol;
• adjusting the content each of the components;
• and
• making the cloud point of the pharmaceutical composition 30° C. to 75° C.;
• whereby stabilizing the emulsified state of the pharmaceutical composition.

A method for evaluating storage stability of a pharmaceutical composition, wherein the pharmaceutical composition comprises components (A), (B), (C), and water,

• the method comprising:
• measuring a cloud point of the pharmaceutical composition;
• determining a difference between the cloud point and a storage temperature of the pharmaceutical composition;
• and
• evaluating the storage stability of the pharmaceutical composition by taking the difference as an index,
• where the components (A), (B), and (C) are as follows:
• Component (A):
• l-menthol;
• Component (B):
• at least one selected from the group consisting of:
• a medium-chain fatty acid triacylglycerol;
• a medium-chain fatty acid;
• and
• a salt of medium-chain fatty acid;
• and
• Component (C):
• a nonionic surfactant having a hydrophile-lipophile balance (HLB) of not less than 10.