Zp. Hu et al., Characterization of norfloxacine release from tablet coated with a new pH-sensitive polymer, P-4135F, J DRUG TAR, 7(3), 1999, pp. 223-232
A new pH-sensitive polymer, P-4135F, was evaluated as a colon delivery devi
ce for norfloxacine (NFLX) which is used for the therapy of patients with V
ero toxin-producing Escherichia coli gastroenteritis. P-4135F has a dissolu
tion 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-413
5F coated tablets with other enteric polymer coatings, mini-tablets contain
ing sodium fluorescein (FL) as a model drug were prepared by coating them w
ith the three polymers. After oral administration of FL mini-tablets to rat
s, the: first-appearance time, T-i, of FL into the systemic circulation was
measured, The T(i)s were 0.7 +/- 0.2 h for Eudragit L100, 1.8 +/- 0.4 h fo
r 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 perfor
med by abdominal incision studies. All of the coated FL mini-tablets starte
d 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 prep
ared and were orally administered to beagle dogs. The colon delivery effici
ency was evaluated by measuring the T-i of NFLX into the systemic circulati
on. The mean T(i)s were 1.33 +/- 0.33 h for 56.8 +/- 0.5 mu m membranes, 3.
75 +/- 0.25 h for 64.6 +/- 0.7 mu m membranes, 4.00 +/- 1.00 h for 70.5 +/-
0.5 mu m membranes and 3.00 +/- 1.00 h for 74.9 +/- 0.4 mu m membranes, Bq
comparing the T-i, 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 reac
hing the colon. Studies using rats and beagle dogs have suggested that P-41
35F dissolves in the lower part of the small intestine, i.e., the ileum. Th
ese studies also suggest that this new polymer will be useful for the deliv
ery of NFLX to the lower part of the small intestine.