ABSTRACT
The aim of the present study was to find the in vivo performance of guar gum-based colon-targeted tablets of ornidazole (dose 250 mg) in comparison with an immediate release tablet of ornidazole (250 mg) in human volunteers. Six healthy volunteers participated in the study, and a cross over design was followed. The plasma concentration of ornidazole was estimated by HPLC. The immediate release tablets of ornidazole produced peak plasma concentration (Cmax of 2171.33+/-278.15 ng/ml) at 2.91+/-0.14 h (Tmax) whereas colon-targeted tablets produced peak plasma concentration (Cmax of 1716.66+/-125.83 ng/ml) at 11.91+/-0.14 h. The delayed Tmax, decreased Cmax, and decreased ka of ornidazole from guar gum-based colon-targeted ornidazole tablets, in comparison with the immediate tablets, indicated that the drug was not released in stomach and small intestine, but targeted to colon. Slow absorption of ornidazole from the less absorptive colon might result in the availability of drug for local action in the colon.
Subject(s)
Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/pharmacokinetics , Galactans , Mannans , Ornidazole/administration & dosage , Ornidazole/pharmacokinetics , Adult , Animals , Antiprotozoal Agents/blood , Antiprotozoal Agents/chemistry , Area Under Curve , Biological Availability , Chromatography, High Pressure Liquid , Cross-Over Studies , Delayed-Action Preparations , Drug Carriers , Galactans/chemistry , Gastrointestinal Contents/chemistry , Half-Life , Humans , In Vitro Techniques , Intestinal Absorption , Mannans/chemistry , Ornidazole/blood , Ornidazole/chemistry , Plant Gums , Rats , SolubilityABSTRACT
The aim of the present investigation is to develop colon targeted drag delivery sytems for tinidazole using guar gum as a carrier in the treatment of amoebiasis. Fast-disintegrating tinidazole core tablets were compression-coated with 55, 65 and 75% of guar gum. All the formulations were evaluated for the hardness, drug content uniformity, and subjected to in vitro drug release studies. The amount of tinidazole released from tablets at different time intervals was estimated by HPLC method. The compression-coated formulations released < 0.5% of tinidazole in the physiological environment of stomach and small intestine. When the dissolution study was continued in simulated colonic fluids, the compression coated tablet with 55% of guar gum coat released 99% of tinidazole after degradation by colonic bacteria at the end of 24 h of the dissolution study. The compression coated tablets with 65 and 75% of guar gum coat released about 67 and 20% of tinidazole, respectively in simulated colonic fluids indicating the susceptibility of the guar gum formulations to the rat caecal contents. The results of the study show that compression coated tinidazole tablets with either 55 or 65% of guar gum coat is most likely to provide targeting of tinidazole for local action in the colon owing to its minimal release of the drug in the first 5 h of physiological environment of stomach and small intestine. The tinidazole compression coated tablets showed no change either in physical appearance, drug content or in dissolution pattern after storage at 40 degrees C/75% RH for 6 months.
