Resolving the physiological conditions in bioavailability and bioequivalence studies: Comparison of fasted and fed state

Schneider, Felix; Grimm, Michael; Koziolek, Mirko; Modeß, Christiane; Dokter, Anne; Roustom, Tarek; Siegmund, Werner; Weitschies, Werner

doi:10.1016/j.ejpb.2016.09.009

Cited by 80 publications

(64 citation statements)

References 8 publications

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“…In contrast to compendial dissolution test methods, the GastroDuo was able to simulate variable gastric emptying kinetics, dynamic pH, and temperature profiles as well as gastric peristalsis. The basis for these simulations were recent in vivo studies that were performed with healthy subjects [3,4,6,19]. For instance, the application of MRI allowed us to describe the kinetics of gastric emptying in high temporal resolution [6], whereas telemetric capsules such as SmartPill provided deeper insights into luminal conditions in terms of pH value, temperature, and pressures [3].…”

Section: Discussionmentioning

confidence: 99%

“…A balloon located between the blades is directly connected to the central axis and can be inflated with different pressures to simulate mechanical stresses acting on the formulation. The magnitude of these stresses is based on recent in vivo investigations with the SmartPill ® [3]. The drug concentrations are constantly measured at two positions: (1) at the outlet of the gastric cell (in-line) to assess changes of drug concentration in the fluid emptied from the simulated gastric compartment and, (2) in the acceptor vessel to determine the sum of dissolved and undissolved drug substance emptied from the gastric cell.…”

Section: Construction and Settingmentioning

confidence: 99%

“…In order to reflect the physiological variability of these factors in the fasted stomach, six test programs (A-F) were defined. The ranges of the physiological parameters that are covered by these test programs were based on recent in vivo studies performed with SmartPill and MRI [3,5,6].…”

Section: Test Programsmentioning

confidence: 99%

“…In all these programs, dynamic temperature and pH profiles were simulated. The simulated profiles were based on recent in vivo data, which were obtained by administering telemetric capsules in the fasted state together with 240 mL of tap water [3]. These measurements clearly showed that both parameters, pH and temperature, follow a distinct profile in the fasted stomach.…”

Section: Test Programsmentioning

confidence: 99%

“…A deeper understanding of the physiological variability of these parameters under the controlled conditions of bioequivalence and bioavailability studies (BE/BA) conducted in accordance with Food and Drug Administration( FDA) and European Medicines Agency (EMA) guidelines [1], Ref. [2] was gained in recent years through different in vivo investigations that aimed at characterizing the physiological conditions in the stomach and the small intestine [3][4][5][6]. These studies revealed that the conditions in the human GI tract can be highly variable and in particular, gastric emptying was shown to be largely dynamic [5].…”

Section: Introductionmentioning

confidence: 99%

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Comparison of In Vitro and In Vivo Results Using the GastroDuo and the Salivary Tracer Technique: Immediate Release Dosage Forms under Fasting Conditions

et al. 2019

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The fasted state administration of immediate release (IR) dosage forms is often regarded as uncritical since physiological aspects seem to play a minor role for disintegration and drug release. However, recent in vivo studies in humans have highlighted that fasted state conditions are in fact highly dynamic. It was therefore the aim of this study to investigate the disintegration and drug release behavior of four different IR formulations of the probe drug caffeine under physiologically relevant conditions with the aid of the GastroDuo. One film-coated tablet and three different capsule formulations based on capsule shells either made from hard gelatin or hydroxypropylmethyl cellulose (HPMC) were tested in six different test programs. To evaluate the relevance of the data generated, the four IR formulations were also studied in a four-way cross-over study in 14 healthy volunteers by using the salivary tracer technique (STT). It could be shown that the IR formulations behaved differently in the in vitro test programs. Thereby, the simulated parameters affected the disintegration and dissolution behavior of the four IR formulations in different ways. Whereas drug release from the tablet started early and was barely affected by temperature, pH or motility, the different capsule formulations showed a longer lag time and were sensitive to specific parameters. However, once drug release was initiated, it typically progressed with a higher rate for the capsules compared to the tablet. Interestingly, the results obtained with the STT were not always in line with the in vitro data. This observation was due to the fact that the probability of the different test programs was not equal and that certain scenarios were rather unlikely to occur under the controlled and standardized conditions of clinical studies. Nonetheless, the in vitro data are still valuable as they allowed to discriminate between different formulations.

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