Effect of encapsulation of mefenamic acid with cationic Eudragit E on its bioavailability and gastric ulcerogenic activity in rabbits.
Encapsulation of mefenamic acid (MFA), a potent non-steroidal anti-inflammatory drug with cationic acrylic resin, Eudragit E, was carried out using a fluidized-bed granulator (Glatt AG). Three drug:polymer ratios were prepared using 50 ml of 1, 2.5 and 5 per cent w/v aqueous suspension of Eudragit to coat 100 mg powdered drug. The bioavailability of the coated and uncoated drug was studied using four groups of animals, each consisting of six male rabbits (2-2.5 kg). Investigations were performed using the rabbits to examine the effects of prolonged administration of the coated and the uncoated MFA with Eudragit E(1 and 5 per cent) in a dose of 100 mg filled in hard gelatin capsules. One capsule was given daily for 30 days. Plasma levels of MFA with Eudragit E were significantly higher than those of drug only. Meanwhile, 5 per cent w/v polymer coating afforded higher drug availability than 2.5 per cent w/v which induced a higher level than 1 per cent w/v. Chronic gastric ulcers with different severities were found in the internal mucosa of all animals. In addition, there were multiple erosions in the glandular mucosa of stomachs of rabbits receiving MFA within the treatment period. IN the control group the gastric photograph was normal in every instance. Despite the extensive morphological damage at the end of treatment, the observed changes in the stomach of rabbits given coated drug is less deleterious than that treated with uncoated drug. The results of this study indicate that the coating of MFA with cationic Eudragit E increases its bioavailability and decreases the probability of ulceration.(ABSTRACT TRUNCATED AT 250 WORDS)
D000180:Acrylic Resins / Q000008:administration & dosage*; D000818:Animals; D001682:Biological Availability; D002214:Capsules; D008297:Male; D008528:Mefenamic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D011109:Polymethacrylic Acids; D011817:Rabbits; D012995:Solubility; D013276:Stomach Ulcer / Q000139:chemically induced*
D000180:Acrylic Resins; D002214:Capsules; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D008528:Mefenamic Acid