Physiological Pharmaceutics

100 Physiological PharmaceuticsFigure 5.20 The effect of pellet density and size of a meal on the gastric emptying ofmultiparticulatesto have adhered to the mucosa, but to have formed large intragastric boluses. Apparentlythat the slow rate of emptying of the polycarbophil was due to the action of the stomachsqueezing the particles together, causing a loss of surface-bound water and forming a largebolus; occasional retropulsion mixed the bolus with the gastric secretions causing some redispersionof particles. The gastric distension produced by the large indigestible mass elicitedthe fed pattern of activity and the fasting peristaltic waves were suppressed.Another gastroretentive system is the magnetic dose form. This usually contains amagnet, or a mass of magnetic material such as a ferrite, in its centre and an externallyplaced magnet serves to anchor the dose form within the body. Drugs which have beendelivered by this method include cinnarizine, acetominophen and riboflavin, all of whichshowed improved bioavailability. The major drawback with this method is that placing theexternal magnet to hold the tablet in the stomach is technically quite difficult. To makemagnetic tablets commercially viable a better method for applying the magnetic field needsto be produced than that currently available.Dose forms that unfurl or expand in the stomach, becoming too large to exit throughthe pylorus, have also been proposed to achieve prolonged gastric residence. Geometricshapes which have been studied include a continuous solid stick, a ring and a planarmembrane. In fasted beagle dogs retention times of over 24 h were reported 91 , but inhumans the time was reduced to 6.5 h in the fed state and 3 h in the fasted state. The mainproblems with this type of system is that they have to exit the stomach eventually, and hencehave to be biodegradable as well as having expanding properties. This can pose severe designrestrictions. In addition, like all sustained release devices, the systems would have to havea high reliability since they would be designed to administer a large dose of drug over anextended period. Adhesion of dosage form to the oesophagus is common, and the possibilityof a device sticking and expanding in the oesophagus is unpleasant to say the least. Swellablesystems would also have to be able to withstand the 80 to 100 mmHg pressures generatedin the human pylorus 22 92 . These combined difficulties have outweighed any potentialadvantaged for manufacturers to date.