RESUMO
Background: NSAIDS are associated with side effects and research should continue for developing safer drugs. This study aims to evaluate newer thiazolidine-4-ones for their anti-inflammatory and ulcerogenic activities in wister rats.Methods: Five groups of wister rats, 6 in each were used. Anti-inflammatory and ulcerogenic activities of diclofenac (30mg/kg), nimesulide (50mg/kg), thia-1 (50mg/kg) and thia-2 (50mg/kg) are compared with control group (4% Gum Acacia). Carrageenin-induced paw edema, formaline induced acute peritonitis and cotton pellet-induced granulomatous tissue formation models were used for evaluating anti-inflammatory activity. After removing cotton pellets with granuloma on 8th day gastric ulcerogenicity was assessed by using macroscopic and microscopic scoring of ulcers.Results: Diclofenac, nimesulide and thia 2 reduced both paw edema and peritoneal exudate volume significantly (p <0.01). Wet weight of cotton pellets reduced significantly (p <0.01) by diclofenac, nimesulide and thia 2. Diclofenac (p <0.01) and thia 2 (p <0.05) reduced dry weight of cotton pellets significantly. nimesulide and thia-1 reduced it by 19.14% and 2.68% respectively and was considered statistically not significant (p>0.05). Nimesulide, thia-1 and thia-2 did not increase gastric ulcer score significantly (p >0.05). Diclofenac increased ulcer score significantly (p <0.01).Conclusions: Thia-2 demonstrated significant anti-inflammatory activity in acute and chronic models. In addition to inhibition of cyclooxygenase pathway, PPAR agonistic activity may be involved in its anti-inflammatory activity. No significant ulcerogenicity was observed on comparing with nimesulide and control. Further in-vitro and in-vivo studies are recommended to confirm the results of this study.
RESUMO
Aims: To formulate sustained release diclofenac potassium tablets based on solidified reverse micellar solution (SRMS) and to evaluate the in vitro and in vivo properties of the tablets. Study Design: Formulation, in vitro and in vivo evaluation of sustained release diclofenac potassium. Place and Duration of Study: Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, Nsukka and Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Nigeria. Methodology: SRMS, consisting of mixtures of phospholipid and triglyceride were prepared in the ratios of 1:1, 2:1 and 1:2 (Phospholipon® 90H: Softisan® 154) respectively. SRMS-based tablets containing 100 mg of diclofenac potassium each were prepared using validated plastic mould. The physicochemical properties of the tablet formulations were studied and compared with the market brands of the drug for sustained release properties. In vitro release was carried out in simulated intestinal fluid (SIF, pH 7.5) using the USP paddle method. Anti-inflammatory, analgesic/anti-nociceptive and ulcerogenic properties of the formulated tablets were studied using adult Wistar rats. Results: The results showed that the physicochemical properties of the tablet formulations were significantly affected by the composition/ratio of the lipid matrix (LM) used (p < 0.05). The hardness of the tablets ranged from 4.55 ± 0.50 to 5.10 ± 0.39 kgf for tablets formulated with LM 1:2 and 1:1 (M3 and M1) respectively. Friability results indicated that all the SRMs tablets exhibited friability values less than 1 %. The erosion time ranged from 35.8 ± 1.10 to 120.3 ± 0.32 min. The release profile of the tablets showed maximum release between 8 – 11 h for all the batches. Diclofenac potassium tablets based on SRMS had good anti-inflammatory and analgesic properties and also inhibited the ulcerogenicity of the NSAID by up to 85 %. Conclusion: Diclofenac potassium tablets based on SRMS could be used for once daily administration.