Liquid pharmaceutical composition for oral administration comprising paracetamol and codeine

摘要

A fixed-dose liquid pharmaceutical for oral administration comprising about 100 mg/mL paracetamol, about 6 mg/mL codeine phosphate, and a pharmaceutically acceptable excipient. The composition preferably contains not more that 0.2 % codeine-N-oxide and not more that 0.1 % 4-aminophenol. The pH of the composition is preferably about 5.4-6.4 and more preferably about 5.6-6.2. The composition may be a solution free of alcohol. The pharmaceutically acceptable excipient may be selected from a cosolvent (preferably about 200-400 mg/mL propylene glycol, about 200-400 mg/mL glycerol, and about 100-300 mg/mL macrogol 400), a buffer (preferably about 0.5-1.5 mg/mL citric acid monohydrate and about 1.5-2.5 mg/mL sodium citrate), a sweetener (preferably about 3-10 mg/mL sucralose), a preservative (preferably about 1-2 mg/mL methyl parahydroxybenzoate and about 0.1-0.5 mg/mL propyl parahydroxybenzaote), an antioxidant (preferably about 0.5-1.5 mg/mL ascorbic acid), a flavour, a colourant, water, or a mixture thereof. Also described is a process of preparing the composition comprising adding and mixing the excipient(s) in water to obtain a solution, heating the solution to 35-45 °C, adding and mixing the paracetamol and codeine phosphate to the solution at 35-40 °C, and cooling the solution below 30 °C before adjusting the volume with water.