The effect of in vivo dissolution, gastric emptying rate, and intestinal transit time on the peak concentration and area-under-the-curve of drugs with different gastrointestinal permeabilities.

PURPOSE: To theoretically investigate the impact of gastric emptying half-time, intestinal transit time and the time for 85% in vivo dissolution on the peak concentration and area-under-the curve of model drugs. METHODS: Simulations were performed using mathematical models of gastrointestinal physiology and pharmacokinetics of model drugs with different gastrointestinal permeability. They were used to investigate the effect of different permutations of gastric emptying times, intestinal transit times, dissolution rates and effective permeabilities on the maximum plasma drug concentration and the area-under-the-curve of immediate release tablets relative to an oral solution (i.e., Cmax(tablet)/Cmax(solution) and AUC(tablet)/AUC(solution)). RESULTS: The higher the permeability of the drug, the more sensitive the Cmax ratio is to dissolution rate and gastric emptying rate. As the intestinal transit time becomes more rapid, the sensitivity to T85% dissolution time and gastric emptying half-time increases. There is less dependence for the AUC ratio on the gastric emptying time and dissolution rate. CONCLUSIONS: Under the assumptions of the models, the criterion of 85% dissolution in 15 minutes (T85%) for classifying a rapidly dissolving drug product is relatively conservative since the Cmax ratio exceeded 0.8 for a T85% dissolution time of one hour and a gastric emptying half-time faster than 0.2 hour over a wide range of permeabilities.

Representation of the path of a non-disintegrating capsule in the gastrointestinal tract using external scintigraphy and computer graphics.

The intestinal transit rate of a single non-disintegrating object has been measured using gamma scintigraphy. Using computer graphics, a three-dimensional visualization of the data has been developed. The display enables viewing from any angle and should be of value in assessing the effect of variables on the transit of pharmaceuticals and other materials.

Effect of stress on the gastric emptying of capsules.

During a series of experiments on the gastric emptying of capsules, certain subjects were exposed to stress in the form of high noise levels. In the non-fasting condition, these subjects showed a significantly faster gastric emptying than those who were not exposed to the stress.