Physiological Pharmaceutics

162 Physiological PharmaceuticsThe first study which employed Eudragit S for colon-targeting used sulphapyridine asa marker for drug release 84 . Hard gelatin capsules containing the drug, and barium sulphateto aid radiological visualisation, were coated with the polymer and administered to 6subjects who each swallowed 6 capsules. Twelve hours after administration, 4 capsules hadbroken in the distal ileum, 23 in the colon and 9 remained intact. The same approach wasused with 5-aminosalicylic acid (5-ASA) but the thickness of the polymer coating wasreduced from 120 to 80 µm 91 . This formed the basis of the commercial formulation of 5-ASA tablet. There has been at least one report of patients taking 5-ASA and reporting thetransit of intact tablets in their stools. This is probably a result of the high pH at which theEudragit S-based coatings dissolve.The study of Eudragit S coated tablets (10 mm diameter) in 7 volunteer subjects usinggamma scintigraphy yielded some interesting results 92 . In some subjects, stasis at theileocaecal junction was noted. Other subjects had rapid transit through the colon, leadingthe authors to speculate whether the variability in transit meant that a pH-based coating wasan unreliable means of delivery to the colon.Recently the potential for pH-sensitive dextran hydrogels to be used as colon-specificdelivery systems has been investigated in vitro 93 94 .TimeThe constancy of transit of dosage forms through the small intestine has been wellestablished. It has been speculated that if a unit could be timed to release drug around fourhours after leaving the stomach, the unit should be at the base of the ascending colon at thetime of drug release. Approaches to achieve targeted colonic delivery based on hydrogeltechnology, exemplified by the Pulsincap delivery system (Figure 7.8), appear to largelysucceed. The Pulsincap comprises an impermeable capsule body containing the drugformulation, sealed at the neck edge with a hydrogel polymer plug 95 . On ingestion, thecapsule becomes exposed to gastric fluids and the water soluble gelatin cap dissolves,allowing the hydrogel plug to hydrate. At a pre-determined and controlled time point afteringestion, the swollen plug is ejected from the capsule body thereby enabling the drugformulation to be released. The time of plug ejection is controlled by the length of thehydrogel plug and its position relative to the neck of the capsule body.Figure 7.8 Enteric-coated Pulsincap dosage form