A comparison of USP 2 and µDISS Profiler™ apparatus for studying dissolution phenomena of ibuprofen and its salts.

Background: Pharmaceutical salts of poorly soluble drugs typically dissolve faster than their corresponding free acid or base, resulting in supersaturation under some circumstances. The key questions relevant to drug bioavailability "does the salt invoke the supersaturated state?" and, if so, "does precipitation occur?" remain. To answer these questions, different types of dissolution equipment are often used at different stages of the development process.

Aim: To compare the dissolution behaviour of ibuprofen and its sodium and lysine salts in the USP 2 apparatus and the µDISS Profiler™ apparatus. The dissolution, supersaturation of the salt forms and precipitation to the free acid of ibuprofen were characterized along with the dissolution of the free acid form.

Methods: Media containing different concentrations of the salt-forming counterions - sodium and lysine - were used to investigate the influence of the type of dissolution apparatus used for the study on dissolution, supersaturation and precipitation behaviour.

Key Results: Supersaturation was observed for both the sodium and lysinate salts of ibuprofen in all USP 2 apparatus and µDISS Profiler™ experiments. However, precipitation tended to be far greater in the µDISS Profiler™ than in the USP 2 apparatus. The difference was most pronounced in pH 4.5 acetate buffer, in which precipitation was observed exclusively in experiments with the µDISS Profiler™.

Conclusion: Choice of dissolution apparatus can affect the dissolution/supersaturation/precipitation characteristics of pharmaceutical salts. This has to be carefully taken into account when investigating salts over different stages of pharmaceutical research and development.