Pharmaceutical composition of piperazine derivatives
View Patent ↗The present invention relates to a liquid composition containing an active substance belonging to the family of substituted benzhydryl piperazines with reduced amounts of preservatives.
1. A liquid pharmaceutical composition comprising (i) levocetirizine or a pharmaceutically acceptable salt of levocetirizine, and (ii) a preservative mixture consisting essentially of a mixture of methyl parahydroxybenzoate and propyl parahydroxybenzoate in a ratio of 9/1 expressed in weight, said mixture being present in an amount of more than 0 and up to 0.75 mg/ml of the composition, wherein said composition is substantially free of bacteria.
2. The liquid pharmaceutical composition according to claim 1 , wherein the composition is aqueous.
3. The liquid pharmaceutical composition according to claim 1 , wherein the amount of the p-hydroxybenzoate esters is in the range of 0.0001 to 0.75 mg/ml of the composition.
4. The liquid pharmaceutical composition according to claim 1 , wherein the composition is in the form of oral solutions, nasal drops, eye drops or ear drops.
5. The liquid pharmaceutical composition according to claim 1 , wherein the pharmaceutically acceptable salt of levocetirizine is a hydrochloride salt.
6. The liquid pharmaceutical composition according to claim 5 , wherein the hydrochloride salt of levocetirizine is present in amount of 0.5 mg/ml and the mixture of methyl p-hydroxybenzoate and propyl p-hydroxybenzoate is present in amount of 0.75 mg/ml.
7. The liquid pharmaceutical composition according to claim 1 , which composition comprises levocetirizine or a pharmaceutically acceptable salt that is at least 95% by weight of the levorotatory enantiomer of cetirizine.
8. A method of making a liquid pharmaceutical composition according to claim 1 comprising mixing levocetirizine or a pharmaceutically acceptable salt thereof with a mixture of methyl p-hydroxybenzoate and propyl p-hydroxybenzoate, wherein the methyl p-hydroxybenzoate and propyl p-hydroxybenzoate are present in a ratio of 9:1.
9. The method according to claim 8 , comprising mixing a pharmaceutically acceptable salt of levocetirizine with a mixture of methyl p-hydroxybenzoate and propyl p-hydroxybenzoate, wherein the methyl p-hydroxybenzoate and propyl p-hydroxybenzoate are present in a ratio of 9:1.
10. The method according to claim 9 , wherein the pharmaceutically acceptable salt of levocetirizine is a hydrochloride salt.
11. The composition of claim 1 , wherein the composition is in the form of an oral solution comprising 0.50 mg/ml levocetirizine dihydrochloride, 0.675 mg/ml methyl p-hydroxybenzoate, and 0.075 mg/ml propyl p-hydroxybenzoate.
12. The composition of claim 1 , wherein the composition is in the form of a solution of oral drops comprising 5.0 mg/ml levocetirizine dihydrochloride, 0.3375 mg/ml methyl p-hydroxybenzoate, and 0.0375 mg/ml propyl p-hydroxybenzoate.