If variability is noted in-vitro with ionic media, then an in-vivo concern should be suspect as well. Diets like the American breakfast or those in which fruit/fruit juice/vitamin consumption is a part would naturally lend variability in release rates from HPMC capsules that contain gelling aids. Simulated milk fluid is routinely used to compare the ionic strength of a fed state against that of the fasted protocol of the pH 1.2 (USP) protocol. Again high variability exists between the dissolution curve of a product with gelling aids that can occur in-vivo between fed and fasted states. Comparatively, HPMC capsules like Capsugel® Vcaps® Plus which contain no gelling agent or gel promoter, regardless of the pH or the ionic strength of dissolution medium used, show minimal variability. The implication becomes clear for the formulator – a system in which variability all but negated relieves many of the concerns that may occur between the laboratory and the clinic.