Figure 5.21—Gastric retention of a suspension of 20-40 pm ion exchange resin (■) compared to 99mTc-DTPA (▲) which is a water soluble marker
One promising method of achieving gastric retention is by the use of micronised ion exchange resins93. Ionic resins are already in use as drug delivery vehicles94, in which release from the resin occurs through the replacement of the drug by another ion of the same charge. Recent studies95 have shown that if micronized resins are administered in a small volume of water, they coat the stomach uniformly, and approximately 20% of the resin is retained for 5-6 hours and is not dislodged by subsequent meals (Figure 5.21). Anionic resins such as cholestyramine have been shown to display better mucoadhesive properties in vitro than cationic polymers96. This was thought to be due to ionic interactions between the highly charged surface of the polymers and the mucus.
Moving from the upright to the supine position markedly effects the emptying of formulations and hence the rate and extent of drug absorption. Bland, unbuffered liquids and pellet formulations empty more slowly from the stomach when the subject is lying down compared to when upright or sitting erect67 97. For floating formulations, such as raft-forming alginates, the buoyant raft empties faster than food in subjects lying on their left side or their backs, and slower in subjects lying on their right side with the raft positioned in the greater curvature98. When the subjects lay on their left side the raft was presented to the pylorus ahead of the meal and so emptied first. Oily materials float and hence also empty more slowly than the aqueous phase of the meal when subjects are in the sitting position28. Posture also affects the emptying of large non-disintegrating capsules from the fasted stomach. Capsules are only passed into the duodenum during phase III of the first MMC initiated when the subjects are lying in the right lateral position99. The gastric residence of floating and non-floating capsules is similar in supine subjects100.
Posture can also affect drug absorption. The time to maximum plasma concentration of coadministered soluble paracetamol, nifedipine, and its metabolite produced at first pass, was significantly decreased when subjects are standing or lying on their right side compared to when they lay on their left side101. These postures also resulted in a significantly higher peak plasma concentration and area under the plasma concentration-time curve of the nifedipine, but not its metabolite. The increased absorption of these drugs also produced a significantly higher heart rate. Lying down decreased the rate of gastric emptying when compared to sitting, and a combination of sitting and standing produced the most rapid gastric emptying102.
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