ACUTE GASTROINTESTINAL TOXIC EFFECTS OF SUSPENSIONS OF UNENCAPSULATEDAND ENCAPSULATED IBUPROFEN IN RATS

Purpose. The study examined the gastrointestinal (GIT) toxicity effect s of suspensions of encapsulated and unencapsulated ibuprofen in male Wistar rats. Methods. Rats were randomly divided into four experimenta l groups and four control groups, and dosed with suspensions of encaps ulated and unencapsulated ibuprofen (17 mg/kg and 44 mg/kg). Bethanech ol chloride, a cholinomimetic agent (5 mg/kg), was administered 30 min utes after the dosing, to induce gastric irritation. Blood plasma conc entrations were monitored in another set of rats for 12 hours using th e encapsulated and unencapsulated systems, to establish drug release a nd exposure to the mucosa. Results. Evaluation of the upper GI segment s after 7 hours revealed that the 44 mg/kg dose of the encapsulated dr ug significantly reduced the number of lesions present compared to the unencapsulated drug (p < 0.05). At 17 mg/kg, the encapsulated drug re duced toxicity, but not significantly compared to the unencapsulated i buprofen. Necrosis of the mucosa was observed histopathologically in t he unencapsulated drug at both doses, whereas the encapsulated drug tr eatment revealed preserved mucosa. The encapsulated system had a maxim um plasma concentration, Cmax, and time taken to reach Cmax, (Tmax) of 26.7 mu g/ml +/- 1.5 and 3.6 +/- 0.2 hr, respectively. The area under the plasma concentration-time curve, (AUC(0-12)), was 158.8 +/- 23.5 mu g . h/ml, confirming drug release and absorption. Conclusions. Enca psulation of ibuprofen significantly reduced gastrointestinal toxicity especially at the higher dose level and drug was released enough to s ubject the GI mucosa to irritation, but without the usual toxic effect s.