Cold water extraction of codeine containing combination analgesics available prescription free in Australia

Cornelia Locher


The abuse of codeine containing combination analgesics leads to significant non-opioid toxicities. Cold water extraction (CWE) reduces these side effects but can also provide access to highly restricted codeine phosphate. This study aims to assess the effectiveness of CWE for a range of drug combinations available on the Australian market as ’pharmacist-only’ medicines. Six products containing codeine phosphate in combination with paracetamol, ibuprofen or aspirin as well as an excipient free mixture of codeine phosphate and ibuprofen lysinate were treated by CWE and the resulting drug content in the filtrate analysed by HPLC. The effect of an additional acidification step was also assessed for combinations containing aspirin and ibuprofen lysinate. It was found that CWE is able to remove almost all ibuprofen (up to 97%), but significant amounts of paracetamol (between 70% and 80% depending on the formulation) and aspirin (nearly 60%) remain in the filtrate. An additional acidification step can reduce the residual amount of dissolved aspirin to about 42%. The substitution of ibuprofen with ibuprofen lysinate allows the removal of the NSAID from the filtrate (via CWE followed by acidification) but lysinate as a water soluble impurity remains.


Cold water extraction (CWE); HPLC; codeine phosphate; codeine containing combination analgesics; ibuprofen lysinate

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