Stereoselective Disposition of Ibuprofen Enantiomer Sustained Release Microspheres in Rats: I. Bioavailability Considerations

Stereoselective Disposition of Sustained Release Microspheres of Ibuprofen Enantiomers in Rats: II. Acute Gastrointestinal Toxicity

“…The plasma concentration time pro les suggest that the drug release from the sustained release (SR) formulation was suitably modi ed and exhibited a bimodal disposition similar to that observed in a previous study (20). The C max of the sustained release formulations was reduced, the T max delayed, and the AUC increased for sustained release as compared with the conventional suspension ( Table 2).…”

“…Reports in the literature suggest that there is a relationship between enterohepatic recirculation and NSAID enteropathy observed in the small intestine (24,25). However, a study was conducted in our lab using bile duct ligated rats to investigate whether the second peak of the bimodal plasma pro le seen for sustained release microspheres could be attributed to either colonic absorption or enterohepatic recirculation (20). This study, concluded that there was no contribution of enterohepatic recirculation to the bimodal pro le.…”

“…Relatively high toxicity was seen in the cecum and the colon as shown in Figures 4 and 5. The pH of the cecum has been reported to be 4.5 at which the solubility of ibuprofen is low (pKa 4.8) (20). Therefore, toxicity seen in the cecum could be due to the local irritant effect of undissolved or recrystallized ibuprofen.…”

“…The microspheres showed sustained release properties with an in vitro T 50 (time at which 50% of the drug is released from a formulation) of 2 hr ( Figure 1A) as reported previously (14,20). A kinetic analysis was carried out to determine the mechanism of drug release from the wax matrix microspheres.…”