A new pH-sensitive
polymer,
P-4135F, was evaluated as a colon delivery device for norfloxacine (NFLX) which is used for the
therapy of patients with
Vero toxin-producing Escherichia coli
gastroenteritis.
P-4135F has a dissolution threshold pH of 7.2 which is higher than the conventional pH-sensitive
polymers,
Eudragit S100 and L100. To compare the dissolution site of
P-4135F coated
tablets with other enteric
polymer coatings, mini-
tablets containing
sodium fluorescein (FL) as a model drug were prepared by coating them with the three
polymers. After
oral administration of FL mini-
tablets to rats, the first-appearance time, Ti, of FL into the systemic circulation was measured. The Tis were 0.7+/-0.2 h for
Eudragit L100, 1.8+/-0.4 h for S100 and 2.0+/-0.3 h for
P-4135F. Direct inspection of the dissolution process of the FL mini-
tablets after
oral administration to rats was performed by abdominal incision studies. All of the coated FL mini-
tablets started to dissolve in the rat ileum. The dissolution sites were identified to be proximal to the ileocecal junction for
P-4135F, at the middle part of the ileum for
Eudragit S100 and at the proximal part of the ileum for
Eudragit L100. NFLX
tablets with different membrane thicknesses of
P-4135F were prepared and were orally administered to beagle dogs. The colon delivery efficiency was evaluated by measuring the Ti of NFLX into the systemic circulation. The mean Tis were 1.33+/-0.33 h for 56.8+/-0.5 microm membranes, 3.75+/-0.25 h for 64.6+/-0.7 microm membranes, 4.00+/-1.00 h for 70.5+/-0.5 microm membranes and 3.00+/-1.00 h for 74.9+/-0.4 microm membranes. By comparing the Ti, 4.33+/-0.33 h, obtained after
oral administration of NFLX in a pressure-controlled colon delivery
capsule, and the colon arrival time, 3.5+/-0.3 h, determined by a
sulfasalazine test in beagle dogs.
P-4135F coated NFLX
tablets appeared to dissolve and disintegrate before reaching the colon. Studies using rats and beagle dogs have suggested that
P-4135F dissolves in the lower part of the small intestine, i.e., the ileum. These studies also suggest that this new
polymer will be useful for the delivery of NFLX to the lower part of the small intestine.