Supercritical fluid extraction-supercritical fluid chromatography of saliva: Single-quadrupole mass spectrometry monitoring of caffeine for gastric emptying studies.

Saliva is an attractive sampling matrix for measuring various endogenous and exogeneous substances but requires sample treatment prior to chromatographic analysis. Exploiting supercritical CO for both extraction and chromatography simplifies sample preparation, reduces organic solvent consumption, and minimizes exposure to potentially infectious samples, but has not yet been applied to oral fluid. Here, we demonstrate the feasibility and benefits of online supercritical fluid extraction coupled to supercritical fluid chromatography and single-quadrupole mass spectrometry for monitoring the model salivary tracer caffeine.

Design and Optimization of a Novel Strategy for the Local Treatment of Helicobacter pylori Infections.

Infections with Helicobacter pylori are a global challenge. Currently, H. pylori infections are treated systemically, but the eradication rates of the different therapy regimens are declining due to the growing number of bacterial strains resistant to major antibiotics.

Application of the GastroDuo to study the interplay of drug release and gastric emptying in case of immediate release Aspirin formulations.

The process of gastric emptying is of major importance for the in vivo performance of immediate release dosage forms. In the fed state, this process consists of two phases: the rapid emptying of water along the "Magenstrasse" and the continuous emptying of the chyme. The relevance of these phases for the pharmacokinetic (PK) profile of a drug depends on the release behavior from its dosage form.

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

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.

In vivo characterization of enTRinsic™ drug delivery technology capsule after intake in fed state: A cross-validation approach using salivary tracer technique in comparison to MRI.

The instability of various small molecules, vaccines and peptides in the human stomach is a complex challenge for oral drug delivery. Recently, a novel gastro-resistant capsule - the enTRinsic™ Drug Delivery Technology capsule - has been developed. In this work, the salivary tracer technique based on caffeine has been applied to study the in vivo disintegration of enTRinsic™ capsules in 16 healthy volunteers.

Application of the GastroDuo as an in Vitro Dissolution Tool To Simulate the Gastric Emptying of the Postprandial Stomach.

In the postprandial stomach, processes such as secretion, digestion, and gastric emptying all occur simultaneously. Therefore, the system is highly heterogeneous and dynamically changing, for instance, in terms of various physicochemical parameters such as pH value or viscosity. Thus, the administration of a drug together with food can result in highly variable drug plasma concentrations, which may affect the efficacy and safety of the pharmacotherapy.

Combined Application of MRI and the Salivary Tracer Technique to Determine the in Vivo Disintegration Time of Immediate Release Formulation Administered to Healthy, Fasted Subjects.

The process of disintegration is a crucial step in oral drug delivery with immediate release dosage forms. In this work, the salivary tracer technique was applied as a simple and inexpensive method for the investigation of the in vivo disintegration time of hard gelatin capsules filled with caffeine. The disintegration times observed with the salivary tracer technique were verified by magnetic resonance imaging (MRI).

Low dose caffeine as a salivary tracer for the determination of gastric water emptying in fed and fasted state: A MRI validation study.

Improving our knowledge about human gastrointestinal physiology and its impact on oral drug delivery is crucial for the development of new therapies and effective drug delivery systems. The aim of this study was to develop an in vivo tool to determine gastric emptying of water by administration of a caffeine as a tracer substance followed by subsequent saliva caffeine analysis. For this purpose, 35 mg of caffeine were given to six healthy volunteers after a 10 h overnight together with 240 mL of tap water either on a fasted stomach or 30 min after the high-caloric, high-fat breakfast recommended for bioavailability/bioequivalence (BA/BE) studies.

Effect of Coadministered Water on the In Vivo Performance of Oral Formulations Containing N-Acetylcysteine: An In Vitro Approach Using the Dynamic Open Flow-Through Test Apparatus.

The drug plasma profile after oral administration of immediate release dosage forms can be affected by the human gastrointestinal physiology, the formulation, and the drug itself. In this work, we investigated the in vivo and in vitro performance of two formulations (granules vs. tablet) containing the highly soluble drug N-Acetylcysteine (BCS class I).

Navigating the human gastrointestinal tract for oral drug delivery: Uncharted waters and new frontiers.

Many concepts of oral drug delivery are based on our comprehension of human gastrointestinal physiology. Unfortunately, we tend to oversimplify the complex interplay between the various physiological factors in the human gut and, in particular, the dynamics of these transit conditions to which oral dosage forms are exposed. Recent advances in spatial and temporal resolution of medical instrumentation as well as improved access to these technologies have facilitated clinical trials to characterize the dynamic processes within the human gastrointestinal tract.