Search

Mefenamic acid (MFA) treatment is associated with a number of cellular effects that potentiate the incidence of renal toxicity. The aim of this study is to investigate the potential ultrastructural alterations induced by various preparations of MFA (free MFA, MFA-Tween 80 liposomes, and MFA-DDC liposomes) on the renal tissues. Sprague-Dawley rats were subjected to a daily dose of MFA preparations for 28 days. Renal biopsies from all groups of rats under study were processed for transmission electron microscopic examination. The findings revealed that MFA preparations induced various ultrastructural alterations including mitochondrial injury, nuclear and lysosomal alterations, tubular cells steatosis, apoptotic activity, autophagy, and nucleophagy. These alterations were more clear in rats received free MFA, and MFA-Tween 80 liposomes than those received MFA-DDC liposomes. It is concluded that MFA-DDC liposomes are less potential to induce renal damage than free MFA and MFA-Tween 80 liposomes. Thus, MFA-DDC liposomes may offer an advantage of safe drug delivery.

The new mefenamic acid-alginate bead formulation prepared by ionotropic gelation method using 3 x 2(2) factorial design has shown adequate controlled release properties in vitro. In the present study, the irritation effects of mefenamic acid (MA), a prominent non-steroidal anti-inflammatory (NSAI) drug, were evaluated on rat gastric and duodenal mucosa when suspended in 0.5% (w/v) sodiumcarboxymethylcellulose (NaCMC) solution and loaded in alginate beads. Wistar albino rats weighing 200 +/- 50 g were used during in vivo animal studies. In this work, biodegradable controlled release MA beads and free MA were evaluated according to the degree of gastric or duodenal damage following oral administration in rats. The gastric and duodenal mucosa was examined for any haemorrhagic changes. Formulation code A10 showing both Case II transport and zero order drug release and t(50) % value of 5.22 h was chosen for in vivo animal studies. For in vivo trials, free MA (100 mgkg(-1)), blank and MA (100 mgkg(-1)) loaded alginate beads (formulation code A10) were suspended in 0.5% (w/v) NaCMC solution and each group was given to six rats orally by gavage. NaCMC solution was used as a control in experimental studies. In vivo data showed that the administration of MA in alginate beads prevented the gastric lesions.

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)