FORMULATION AND EVALUATION OF PH-DEPENDENT COLON-TARGETED TABLETS OF RIFAXIMIN BY DESIGN OF EXPERIMENT

Objective: The research is designed at formulating and evaluating pH-sensitive rifaximin colon-targeted tablets for targeted action in proximal colon. Method: The colon-targeted tablets are done by granulation of three levels of polymers such as Eudragit L30D, Carbopol 974P, and ethyl cellulose. The evaluation parameters such as swelling studies, drug dissolution, in vitro drug release studies, stability, and the Fourier transform infrared studies carried out for optimized formulations. Results: Physicochemical parameters of all the 27 formulations (RF1-RF27) evaluated and RF21 is chosen for further investigation based on weight variation, hardness, drug content, and swelling index. The in vitro drug release studies indicate that the optimized formulation RF21 released 98.75% drug within 24 h. The stability studies indicate that the formulation is stable. Conclusion: An effective and stable pH-dependent rifaximin colon-targeted tablet formulated for the targeted treatment of bowel syndrome

Antinociception produced by Thalassia testudinum extract BM-21 is mediated by the inhibition of acid sensing ionic channels by the phenolic compound thalassiolin B

<p>Abstract</p> <p>Background</p> <p>Acid-sensing ion channels (ASICs) have a significant role in the sensation of pain and constitute an important target for the search of new antinociceptive drugs. In this work we studied the antinociceptive properties of the BM-21 extract, obtained from the sea grass <it>Thalassia testudinum</it>, in chemical and thermal models of nociception in mice. The action of the BM-21 extract and the major phenolic component isolated from this extract, a sulphated flavone glycoside named thalassiolin B, was studied in the chemical nociception test and in the ASIC currents of the dorsal root ganglion (DRG) neurons obtained from Wistar rats.</p> <p>Results</p> <p>Behavioral antinociceptive experiments were made on male OF-1 mice. Single oral administration of BM-21 produced a significant inhibition of chemical nociception caused by acetic acid and formalin (specifically during its second phase), and increased the reaction time in the hot plate test. Thalassiolin B reduced the licking behavior during both the phasic and tonic phases in the formalin test. It was also found that BM-21 and thalassiolin B selectively inhibited the fast desensitizing (τ < 400 ms) ASIC currents in DRG neurons obtained from Wistar rats, with a nonsignificant action on ASIC currents with a slow desensitizing time-course. The action of thalassiolin B shows no pH or voltage dependence nor is it modified by steady-state ASIC desensitization or voltage. The high concentration of thalassiolin B in the extract may account for the antinociceptive action of BM-21.</p> <p>Conclusions</p> <p>To our knowledge, this is the first report of an ASIC-current inhibitor derived of a marine-plant extract, and in a phenolic compound. The antinociceptive effects of BM-21 and thalassiolin B may be partially because of this action on the ASICs. That the active components of the extract are able to cross the blood-brain barrier gives them an additional advantage for future uses as tools to study pain mechanisms with a potential therapeutic application.</p

Oxidative stress and antioxidant status in acute organophosphorous insecticide poisoning

Objective: To study the antioxidant status and the extent of oxidative stress in patients with organophosphorus insecticide (OPI) poisoning before and after specific treatment. Material and Methods: The study was conducted in eighty-four OPI poisoned patients. Superoxide dismutase (SOD) and malonyl aldehyde (MDA) levels were estimated as an index of antioxidant status and oxidative stress respectively and comparisons were made (a) between different grades of poisoning based on clinical features and anticholinesterase (AChE) levels, (b) before and after therapy with atropine sulfate plus pralidoxime (PAM) and (c) between healthy control subjects and OPI poisoned patients. Results: There was a progressive fall in both the RBC and plasma AChE levels which correlated with the severity of poisoning. Upon therapy, profound improvement in the AChE levels was observed (an increase by 20.5% and 20.9% in RBC and plasma AChE levels respectively). There was also an increase in the MDA levels which nearly doubled in OPI poisoned patients who failed to survive (3.6 + 0.92 to 6.7 + 2.3 nM/ml). SOD levels increased parallel to the severity of poisoning, but did not normalize after therapy. Conclusion: The increased level of MDA in OPI poisoned patients who failed to survive was probably reflective of accelerated lipid peroxidation, cell damage and death (oxidative stress). Significant improvement was noticed in the AChE (serum and RBC) levels of patients with specific treatment but without much change in the antioxidant status as reflected by the SOD and MDA levels