Characterization of Norfloxacine Release from Tablet Coated with a New pH-Sensitive Polymer, P-4135F

Abstract

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.

FK506 Microparticles Mitigate Experimental Colitis with Minor Renal Calcineurin Suppression

“…Compared to the other pH-sensitive polymers, Eudragit P-4135F dissolves at a pH around 7.2, allowing a further retention of drug release toward the colonic tissue (18,19). This report evaluates the mitigating potential of FK506 in IBD when delivered locally to the colon after oral administration by a microparticulate delivery system based on Eudragit P-4135F.…”

In vitro drug release and in vivo human X-ray studies of ileo-cecal targeting budesonide fast disintegrating tablet

“…The pH in the terminal ileum could rise to 7.5; hence, the delivery devices coated with these polymers have a tendency to release their drug load before reaching the colon, and are more appropriately defined as ileo-colonic delivery systems 10 . A recently developed copolymer of methyl acrylate, methyl methacrylate, and methacrylic acid 11,12 is commercially available as Eudragit ® FS 30 D 10 . This polymer has a similar threshold dissolution pH as Eudragit ® S, but dissolves in a slower and more controlled manner 13 .…”

Site‐Specific Drug Delivery to the Middle Region of the Small Intestine by Application of Enteric Coating with Hypromellose Acetate Succinate (HPMCAS)

“…and to deliver peptides and proteins to the colon for systemic absorption. 5 Strategies for delivering orally administered drugs to the colon include the use of prodrugs, 6 colon-specific biodegradable polymers, 7-9 coatings with pH-sensitive polymers, [10][11][12][13][14][15] and timed-release systems. [16][17][18] However, in some delivery systems, especially those by using pH-sensitive polymers, drugs were released in the terminal ileum before dosage forms reached the colon.…”

“…[16][17][18] However, in some delivery systems, especially those by using pH-sensitive polymers, drugs were released in the terminal ileum before dosage forms reached the colon. For example, it has been shown that tablets coated with Eudragit P-4135F, a new pH-sensitive polymer with a dissolution threshold pH of 7.2, disintegrated in the lower region of the small intestine of rats, 13 and polymeric microspheres of Eudragit P-4135F encapsulating ellagic acid could deliver the drug to the terminal ileum and the colon. 14 We have already developed hypromellose acetate succinate (HPMCAS, Fig.…”