High inter- and intra-individual variability in the pH of fluids in the human gastrointestinal (GI) tract has been described in the literature. The aim of this study was to assess the influence of physiological variability in fasted pH profiles of media along the GI tract on diclofenac sodium (DF-Na) dissolution from matrix tablets. Four individual in vivo fasted pH profiles were selected from the literature that differed in pH values and transit times from the stomach to the proximal colon. Using a glass-bead device flow-through dissolution system, these pH profiles were simulated in vitro using a specific media sequence and considering simulated intestinal buffer capacities corresponding to in vivo literature data. Dissolution experiments were then performed in the same system with media sequence following individual pH profiles. In dissolution experiments, where influences of simulated gastric emptying time (GET), gastric pH value, small intestinal transit time, and colonic pH were studied; high influence of gastric pH value and GET on DF-Na dissolution was observed. The effect of variability in pH profiles in the range of individual in vivo data on DF-Na dissolution was also clearly observed in experiments, where dissolution studies were performed following three simulated in vivo individual pH profiles. The differences in DF-Na release between three individual pH profiles were substantial; they also reflected in simulated plasma concentration profiles and can be attributed to pH dependent diclofenac solubility.
Visualization techniques are frequently used to provide additional information on dissolution processes. The camera system used here, placed underneath the dissolution bath, enabled a bottom view into each separate vessel with the possibility for continuous video recording throughout dissolution testing. Drug release and swelling of hydroxypropyl methylcellulose (HPMC) matrix tablets containing either diclofenac sodium or paracetamol were simultaneously evaluated in a series of media with pH values of 3.0 to 7.5. Swelling of HPMC tablets was studied using two methods: evaluation of the relative change in tablet volume using the camera system and evaluation of relative change in tablet mass based on tablet weighing. The correlation between evaluated parameters in the two methods was high at all pH values for the tablets studied. Swelling of diclofenac sodium tablets was lowest at pH 3, highest at pH 4, and then decreased with the increasing pH of the medium. In contrast to the swelling results, drug release from diclofenac sodium tablets increased with increasing pH of the medium. At lower media pH values (i.e., 3.0, 4.0, and 5.0), the surface of the swelled layer appeared completely white and nontransparent, whereas at higher pH values, a transparent gel layer was clearly seen using the camera system. It is presumed that because of its low solubility, diclofenac precipitated as an acid on the tablet surface at lower pH values and was seen as a white swelled layer. For paracetamol tablets, drug release and swelling were pH independent, and a gel layer was clearly seen in all media tested (pH 3.0, 5.0, and 7.0). Thus, for HPMC tablets containing diclofenac sodium, the use of cameras provided additional information on the drug release and swelling process.
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