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. 2023 Nov 4;15(11):2584.
doi: 10.3390/pharmaceutics15112584.

Determination of Gastric Water Emptying in Fasted and Fed State Conditions Using a Compression-Coated Tablet and Salivary Caffeine Kinetics

Theodora Tzakri  1 , Lara Rehenbrock  1 , Stefan Senekowitsch  1 , Adrian Rump  1 , Philipp Schick  1 , Julius Krause  1 , Marie-Luise Kromrey  2 , Michael Grimm  1 , Werner Weitschies  1
Affiliations

Determination of Gastric Water Emptying in Fasted and Fed State Conditions Using a Compression-Coated Tablet and Salivary Caffeine Kinetics

Theodora Tzakri et al. Pharmaceutics. .

Abstract

Because of the importance of gastric emptying for pharmacokinetics, numerous methods have been developed for its determination. One of the methods is the salivary tracer technique, which utilizes an ice capsule containing caffeine as a salivary tracer. Despite the ice capsule's advantage in labeling ingested fluids with caffeine for subsequent salivary detection, its risk of premature melting before swallowing, and its complicated storage and preparation, limit its application, particularly in special populations (e.g., older people). For this reason, here, a compression-coated tablet was developed and validated against the ice capsule in a cross-over clinical trial. The two dosage forms were administered simultaneously to 12 volunteers in an upright position under fasted and fed state conditions. To distinguish the caffeine concentrations in saliva from each dosage form, regular type of caffeine (12C) was added to the tablet, while for the ice capsule 13C3 labelled caffeine was used. The salivary caffeine concentrations showed no statistically significant differences for the pharmacokinetic parameters tmax and AUC0→60 (p > 0.05). Thus, the new formulation is a useful tool for determining gastric emptying that can also be used in special populations.

Keywords: caffeine; compression-coated tablet; fasted and fed state conditions; gastric emptying; in vivo study; salivary tracer technique.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Timeline of the study day with specific events and saliva sampling time points for both study arms. The fasted state arm did not include meal ingestion. The star refers to the time segment from 0 to 60 min.
Figure 2
Figure 2
Exemplary images of the two formulations: (a) Compression-coated tablets cut in the middle; (b) size comparison of the ice capsule (left) and the compression-coated tablet (right) on millimetre paper.
Figure 3
Figure 3
Dissolution profiles over time in 300 mL SGFsp pH 1.2 at 25 ᵒC and 25 rpm: (a) Comparison of the caffeine release of the tablet and the ice capsule (n = 3, mean—standard deviation); (b) caffeine release of the tablets after 3 months of stability studies (n = 3, mean—standard deviation).
Figure 4
Figure 4
Normalized salivary caffeine concentrations of the compression-coated tablet (black) and the ice capsule (red) over time after their administration together with 240 mL tap water. Each graph shows data of each individual volunteer and the corresponding Pearson’s correlation coefficient (r).
Figure 5
Figure 5
Normalized salivary caffeine concentrations of the compression-coated tablet (black) and the ice capsule (red) over time after their administration together with 240 mL tap water 30 min after intake of the FDA standard meal. Each graph shows data of each individual volunteer and the corresponding Pearson’s correlation coefficient (r).
Figure 6
Figure 6
Mean curves of the normalized salivary caffeine concentrations (n = 12, mean +/− standard deviation) after administration of the two dosage forms in (a) fasted state and (b) fed state.
Figure 7
Figure 7
Distribution of tmax (min) and normalized AUC0→60 (%/min) after administration of the two dosage forms (tablet (black) and ice capsule (red)) with 240 mL water in fasted and fed state conditions (n = 12). The individual data are represented as points and the mean value is depicted as a straight line: (a) tmax in fasted state ranges, i.e., tablet, 14–50 min and ice capsule, 14–50 min (b) tmax in fed state ranges, i.e., tablet 16–150 min and ice capsule 18–240 min (c) AUC0→60 in fasted state ranges, i.e., tablet 3237–4580%/min and ice capsule 3579–4812%/min; (d) AUC0→60 in fed state ranges, i.e., tablet 3124–4869%/min and ice capsule 3190–4811%/min.
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