Ibuprofen is only very slightly soluble in water, less than 1 mg of ibuprofen dissolves in 1 ml water (< 1 mg/mL). However, it is much more soluble in alcohol/water mixtures.
Stereochemistry
Ibuprofen, like other 2-arylpropionate derivatives (including ketoprofen, flurbiprofen, naproxen, ''etc''), contains a stereocenter in the α-position of the propionate moiety. As such, there are two possible enantiomers of ibuprofen, with the potential for different biological effects and metabolism for each enantiomer.
Indeed it was found that (''S'')-(+)-ibuprofen (dexibuprofen) was the active form both ''in vitro'' and ''in vivo''.
It was logical, then, that there was the potential for improving the selectivity and potency of ibuprofen formulations by marketing ibuprofen as a single-enantiomer product (as occurs with naproxen, another NSAID).
Further ''in vivo'' testing, however, revealed the existence of an isomerase (''2-arylpropionyl-CoA epimerase'') which converted (''R'')-ibuprofen to the active (''S'')-enantiomer. Thus, due to the expense and futility that might be involved in making a pure enantiomer, most ibuprofen formulations currently marketed are racemic mixtures.
Synthesis
The synthesis of this compound is a popular case study in green chemistry. The original Boots synthesis of ibuprofen consisted of six steps, started with the Friedel-Crafts acetylation of isobutylbenzene. Reaction with ethyl chloroacetate (Darzens reaction) gave the α,β-epoxy ester, which was decarboxylated and hydrolyzed to the aldehyde. Reaction with hydroxylamine gave the oxime, converted to the nitrile, then hydrolyzed to the desired acid.
An improved synthesis by BHC required only three steps. This improved synthesis won the Presidential Green Chemistry Challenge Greener Synthetic Pathways Award in 1997.
After a similar acetylation, hydrogenation with Raney nickel gave the alcohol, which underwent palladium-catalyzed carbonylation:
Europe
For some time, there has been a limit on the amount that can be bought over the counter in a single transaction in the UK. Behind the counter in pharmacies this is one pack of 96 × 200 mg or 400 mg, the latter being far less common for over the counter sales. In UK non-pharmacy outlets only 200 mg tablets are allowed and they are restricted to a maximum pack of 16 tablets.
In Germany, 600 mg and 800 mg per pill packages have to be prescribed, whereas 400 mg is available over the counter in pharmacies. In Italy, Belgium and the Netherlands, 200 mg and 400 mg pills are available with no prescription.
In other countries, higher dosages of 600 mg are available.
Further Reading
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