Characterization of norfloxacine release from tablet coated with a new pH-sensitive polymer, P-4135F.
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.
Hu
Z
Z
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Japan.
Shimokawa
T
T
Ohno
T
T
Kimura
G
G
Mawatari
S S
SS
Kamitsuna
M
M
Yoshikawa
Y
Y
Masuda
S
S
Takada
K
K
D000180:Acrylic Resins; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D003106:Colon / Q000378:metabolism; D004285:Dogs; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008297:Male; D008689:Methacrylates / Q000737:chemistry*; D009643:Norfloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids; D051381:Rats; D017208:Rats, Wistar; D013608:Tablets, Enteric-Coated
D000180:Acrylic Resins; D000890:Anti-Infective Agents; D005079:Excipients; D008689:Methacrylates; C406272:P-4135F polymer; D011108:Polymers; D011109:Polymethacrylic Acids; D013608:Tablets, Enteric-Coated; C038300:methylmethacrylate-methacrylic acid copolymer; D009643:Norfloxacin