Gastrointestinal transit of dosage forms
This thesis describes the results from a series of studies designed to evaluate the gastrointestinal transit of oral dosage forms. The transit of placebo pellet and tablet formulations was monitored using the technique of gamma scintigraphy. The formulations were radiolabelled with either technetium-99m or indium-lil. Four parameters, two physiological and two pharmaceutical, were selected for investigation. All the studies were conducted in healthy male volunteers. The first study examined the influence of the supine position on the gastric emptying of pellets in fasted and fed subjects. There was no marked difference between the supine and control gastric emptying data. As would be expected, food had a significant effect on gastric emptying. The influence of the time of day of administration on the gastrointestinal transit of pellets was investigated in fasted subjects. Transit of the pellets was not affected by their time of administration. The effect of the putative bioadhesive, polycarbophil, on the gastrointestinal transit of a pellet formulation was studied in fasted subjects. The pellets emptied from the stomach, rapidly and in an exponential manner. A set of studies was conducted to evaluate the transit of tablets in fed and fasted subjects. Tablet size did not affect gastric emptying, although there was an increase in the variability of gastric emptying with increasing tablet size. Food had a marked effect on gastric emptying. The rate of emptying was related to the energy content of the meal. Tablet size did not appear to be a determinant of transit through the ileocaecal sphincter. The colon transit and dispersion of the tablets was examined. Neither the ingestion of food nor defecation appeared to alter the rate of transit through the colon.