Neena Washington

Intragastric Distribution of Ion‐exchange Resins: a Drug Delivery System for the Topical Treatment of the Gastric Mucosa

Previous studies by this group on freeze‐dried oral dosage forms containing finely‐divided ion‐exchange resins revealed prolonged gastric residence and uniform distribution within the stomach. The present study was carried out to ascertain whether this was due to freeze‐drying, properties of the radiolabeled ionic exchange resin, or the small dosing volume used. 99mTc‐labelled cholestyramine resin was administered in two dosage forms, a freeze‐dried tablet which dissolved in the oral cavity (orally dissolving tablet; ODT) and a 1.5 mL aqueous suspension. Two resin particle sizes (20–40 and 90–125 μm) were studied. Oesophageal transit and intragastric distribution and residence were followed by gamma scintigraphy. In a second study, in six subjects, gastric emptying of the water‐soluble fraction of the ODT and 1.5 mL of water, was measured using 99mTc diethylenetriaminepentaacetic acid.

Assessment of Disintegration and Dissolution of Dosage Forms In Vivo Using Gamma Scintigraphy

AbstractThe measurements of the in vitro rate of disintegration and dissolution of dosage forms are considered to be the most available predictors of the behaviour of dosage forms and the plasma concentration - time profile. However, the interaction of the formulation with physiological processes has shown that prediction of bioavailability by such simple tests is inadequate and has highlighted the need to establish methodology which would enable the determination of in vivo rates of dissolution and disintegration. Over the past ten years, the technique of gamma scintigraphy has made a significant contribution to the understanding of the behaviour of formulations in the body. This review provides an overview of the technique and its advantages and limitations in pharmaceutical research, together with illustrations showing some of the applications in the measurement of disintegration and dissolution of dosage forms.

Investigation into the Barrier Action of an Alginate Gastric Reflux Suppressant, Liquid Gaviscon®

SummaryThe barrier properties of an alginate antireflux agent (Liquid Gaviscon®, Reckitt and Colman, UK) were investigated using a portable cadmium telluride detector worn on the chest wall over the oesophagus to detect the reflux of radiolabelled food, with simultaneous oesophageal pH monitoring. A crossover study was performed in 12 healthy nonpatient volunteers.An oesophageal pH probe was placed coincident with a small γ-detector strapped to the chest wall and the positioning verified using γ-scintigraphy. A test meal designed to promote reflux was radiolabelled and administered to the subjects. On 1 occasion, subjects received only the meal, and on the second occasion the subjects also received a 20ml dose of alginate antireflux agent (Liquid Gaviscon®) 30 minutes after the meal had been consumed. The reflux of radiolabel and acid was monitored for 3 hours post-prandially.The antireflux agent was found to significantly reduce the amount of both acid and food reflux. The length of time for which the pH in the oesophagus was below 4 was 19.9 ± 1.6 minutes (mean ± SEM) in the untreated group, but 3.0 ± 4.0 minutes for the treated group. Although the absolute amounts of acid refluxed cannot be measured, it is possible to estimate the ratio of amounts of acid refluxed in treated and untreated groups. This ratio was 0.119 ± 0.028, indicating that the antireflux agent prevented the reflux of 88% of the acid refluxed by the untreated group. The ratio of the amount of food reaching the oesophagus in treated and untreated groups could be similarly estimated from the refluxed activity data as 0.095 ± 0.024, indicating suppression of food reflux by 90%. This study demonstrates that Liquid Gaviscon® significantly reduces the reflux of both food and acid.

The influence of food on the absorption of acyclovir: a pharmacokinetic and scintigraphic assessment

Abstract The effects of a light or heavy breakfast on the absorption of acyclovir (400 mg), containing technetium-99m labelled resin and administered as a suspension to 6 healthy volunteers, has been followed using gamma scintigraphy and measurement of plasma concentration. The heavier meal slowed the rate of gastric emptying, prolonged small intestinal transit time and significantly decreased absorption of the drug. No correlation was found between the small intestinal transit time and the area under the plasma concentration time curve.

Effect of time of dosing relative to a meal on the raft formation of an anti‐reflux agent

Abstract— Gamma scintigraphy was used in twelve healthy volunteers to establish whether the time of dosing of Liquid Gaviscon relative to a meal influenced its therapeutic action. Indium‐113m labelled Liquid Gaviscon was administered to fasted subjects, 30 min after a technetium‐99m labelled meal or immediately before ingestion of the meal. The time for 50% of the Gaviscon to empty from the stomach was 0.36 ± 0.13 h, 3.10 ± 0.31 h and 0.68 ± 0.04 h (s.e.m.), respectively. The preparation was found to empty rapidly from the fasted stomach and could not be floated on a meal consumed subsequently. For raft formation to occur, Liquid Gaviscon should be taken 30 min after a meal.

Effect of Alginate and Alginate-cimetidine Combination Therapy on Stimulated Postprandial Gastro-oesophageal Reflux

This randomized, single‐blind cross‐over study compared the effectiveness of a conventional alginate reflux barrier formulation (20 mL single dose of Liquid Gaviscon; sodium alginate, sodium bicarbonate, calcium carbonate) with a 20 mL single dose of an alginate‐cimetidine combination formulation (Algitec Suspension; sodium alginate, cimetidine) in the suppression of food and acid reflux into the oesophagus after a test meal in 12 healthy volunteers.