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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. 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. 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. 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™. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

Liquid-liquid phase separation (LLPS) plays a pivotal role in processes ranging from cellular structure reorganization to the formation of crystalline structures in materials science. In the pharmaceutical field, it has been demonstrated to impact drug crystallization and delivery. To date, characterization of LLPS has been limited to nonspatially resolved or nonchemically resolved analyses. In this study, we employed chemically specific stimulated Raman scattering (SRS), combined with second harmonic generation (SHG), for the first time to image crystallization in the presence of LLPS. Using the model compound ibuprofen, we examined the interplay between LLPS and crystallization, and explored the influence of both dissolution medium and enantiomeric form on this behavior. In doing so, we also discovered and partially characterized a new polymorph of (S)-ibuprofen. Our results demonstrate the potential of correlative SRS and SHG for monitoring phase separation and crystallization in real time, giving mechanistic insights into the spatial distribution, chemical composition and structure of phase-separated domains and newly formed crystals. Such insights could benefit not only pharmaceutical development, but also the biomedical, food and chemical sectors.