Gastrointestinal transit of model mini-tablet controlled release oral dosage forms in fasted human volunteers.

The aim of this study was to compare the gastrointestinal transit of multiple unit, small diameter (3.2 mm), non-disintegrating tablets of differing densities with results previously reported in the same volunteers in the fasted state for larger diameter (6.6 and 12.2 mm) tablets. The gastrointestinal transit was observed with gamma-scintigraphy at various intervals over a 9-h period to give an accurate assessment of the transit characteristics. The value for the median emptying time of the first light tablet was significantly shorter than that for the dense tablet, but the total emptying time and the time for the last tablet to empty for both sets of tablets were not statistically different. The value of the median time for initial and final emptying of the small tablets from the stomach was significantly longer than that for the larger diameter tablets. The 9-h time limit of the observations limited the estimation of the time taken to enter the caecum and consequently the small intestine transit times. There was clear evidence that for the dense tablets of all sizes, the value for the small intestine transit time was longer than the 3-4 h reported in the literature. The only tablet system to enter the caecum within the time limit of the study was the normal density 12.2-mm tablets.

The influence of non-disintegrating tablet dimensions and density on their gastric emptying in fasted volunteers.

The aim of this work was to identify the influence of tablet density on their gastric emptying in fasted subjects and to compare the findings with those of a previous study using the same subjects with tablets of a larger diameter. Tablets of 6.6 mm diameter and densities of 1.41 and 2.85 g cm-3 were labelled with 99mTc and 111In. They were coated with ethyl cellulose to ensure that they remained intact within the gastrointestinal tract. Their position within the gastrointestinal tract of fasted healthy subjects was monitored with a double-headed gamma camera at 1-min time intervals. The median gastric emptying time and the interquartile range were derived from the Bernoulli random event distribution. It was found that the dense tablets had a significantly longer gastric emptying time than the light tablets. Comparison with the results from the previous study gave a clear indication that irrespective of tablet density, the 6.6-mm tablets had longer gastric emptying times than the 12.0-mm tablets.

Stomach outline visualization in gastrointestinal transit studies using scintigraphy.

A major disadvantage of gamma scintigraphy in gastrointestinal transit studies is the inability to provide adequate delineation of anatomical details. As an aid to the important requirement of outlining the stomach to ensure accurate quantification of the time at which material empties from this organ, a new technique is described, using short half-life 81mKr gas to provide clearer identification of the stomach outline and position.

Determination of the gastric emptying of solid dosage forms using gamma-scintigraphy: a problem of image timing and mathematical analysis.

This work was designed to identify the maximum time interval of image acquisition by gamma-scintigraphy for monitoring the emptying of a dosage form such as a tablet. Appropriate statistical parameters to describe this process were sought, including a statistical procedure for group comparisons of such data. Gamma-scintigraphy was employed in seven healthy male volunteers, who swallowed a light and a dense tablet, each 12 mm in diameter, formulated to contain different isotopes to allow identification. Images were taken sequentially at 30-s intervals to provide images of each tablet in 1-min spacing until emptying of both tablets was reported. In selecting images, it was also possible to simulate image acquisition intervals of 2, 3, 5, 10, 15, 20 and 30 min. The values derived are discrete random variables. The maximum time interval between image acquisitions that permitted reliable results to be obtained was found to be 3 min for light and 2 min for dense tablets. Consideration of the emptying of a tablet as a Bernoulli random event provided a suitable statistical approach to the analysis of such data, giving a median and an interquartile range. While the commonly applied method, which is based on parametric procedures deriving arithmetic means and standard deviations, failed to detect a difference in the emptying times of the two types of tablets, the use of non-parametric statistics (Wilcoxon test) provided a clear distinction between them in this respect. The assessment of gastric emptying by gamma-scintigraphy studies can be improved by using short image intervals and application of appropriate statistical analysis.