In vivo studies of amylose- and ethylcellulose-coated [C-13]glucose microspheres as a model for drug delivery to the colon

The observation that certain starches naturally present in the diet resist pancreatic enzymes and reach the colon where they are fermented by bacterial amylases has been exploited to provide a coating for specifically targeting drugs to the human large intestine. A mixture of amylose, which is a fraction of starch that can be made resistant to pancreatic enzymes, and Ethocel (1:4 amylose:Ethocel) has been developed and [C-13]glucose used as a surrogate for drug delivery. Eight healthy subjects were given, fasting, at 8 am amylose-Ethocel coated pellets containing 300 mg [C-13]glucose together with a further capsule that contained amberlite resin labelled with Tc-99m to act as a transit marker and outline for the anatomy of the gut. Subjects underwent gamma-scintigraphy at half-hourly intervals for 5 h and then at hourly intervals until 8 pm. Breath samples were taken for (CO2)-C-13, which was measured by gas isotope mass spectrometry, at half-hourly intervals for 5 h and then hourly until 2300 h, with two further breath samples the following morning before breakfast. Gamma-scintigraphy showed that 5% of the activity had arrived in the caecum at 3.5 h after oral dosage (range 2.5-4.75 h) with all the material in the colon after 7.1 h (4.5-10 h). Breath (CO2)-C-13 data were analysed by the cusum technique and by curve fitting to determine first appearance of (CO2)-C-13 in breath. The first rise in breath (13)CO2 was at 3.5 h (range 2.0-6.0 h) with 1% accumulated recovery of breath (CO2)-C-13 at 6.2 h (5.2-7.3 h). Total (CO2)-C-13 recovery at 25 h was 37.5% (21.9-47.8%). A single subject given a dose of uncoated glucose showed a rise in breath (CO2)-C-13 at 30 min peaking at 1.5 h and a total recovery of 28% at 6 h. Accumulated recovery curves for (CO2)-C-13 in breath showed that pellet breakdown and glucose metabolism was occurring over a 15 h period with a delay of about 2.7 h between arrival in the caecum and significant (1%) breakdown of the pellets. Resistant amylose, a naturally occurring component of the diet combined with ethylcellulose, can therefore be used to coat pellets that allow controlled release of contents for targeted drug delivery to the large bowel during a 12-24 h period.