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

Abstract

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.

Novel Biphasic Lipolysis Method To Predict in Vivo Performance of Lipid-Based Formulations

“…In the biphasic lipolysis setup, the switch from gastric to intestinal conditions occurs very rapidly, whereas in vivo the process of gastric emptying is usually more gradual. 34 This rapid pH transition may lead to an overestimation of the precipitation rate. Also, the 1 min delay after transition to pH 7.5, included to facilitate dispersion of the pancreatic enzyme prior to the addition of decanol, indicates that permeation during the initial transient supersaturation period upon shift to intestinal conditions may not have been fully captured by the decanol concentration profile.…”

Determination of healthcare resource and cost implications of using alternative sodium valproate formulations in the treatment of epilepsy in children in England: A retrospective database review

“…Drug absorption occurs to the greatest extent within the small intestine; thus the rate of drug absorption will depend not only on the mechanisms built into the formulations but also the rate at which the formulations reach the small intestine. Previous work has demonstrated that small units (pellets or minitablets) reach the small intestine more rapidly than single large units (tablets) [27]; yet other work has contradicted this finding [28]. However, in both studies a single tablet of >3mm was used.…”

Is it possible to achieve bio-equivalence between an oral solid immediate-release and an analogue enteric-coated formulation?

“…The kinetics of gastric emptying is a crucial factor in the gastrointestinal transit of oral dosage forms. Gastric emptying is affected by factors such as the shape and size of the dosage forms administered orally, prandial state, meal composition and posture . For monolithic enteric‐coated dosage forms, gastric emptying time under fasted conditions corresponds to the ‘housekeeper wave’ in the migrating motor complex (MMC) .…”

“…Gastric emptying is affected by factors such as the shape and size of the dosage forms administered orally, prandial state, meal composition and posture. [5][6][7][8][9][10][11][12] For monolithic enteric-coated dosage forms, gastric emptying time under fasted conditions corresponds to the 'housekeeper wave' in the migrating motor complex (MMC). [13] There appears to be a link between the gastric emptying kinetics, pharmacokinetic profile and tablet size of non-disintegrating dosage forms.…”