Baclofen was well tolerated, safe, and effective in the treatment of muscle cramps in patients with liver cirrhosis.

Objective: The present investigation aims to formulate and evaluate proniosomes of clopidogrel bisulphate for improving its dissolution characteristics. Methods:The slurry method was used for the preparation of proniosomes of clopidogrel using cholesterol, sorbitan monostearate (Span 60) and maltodextrin as a carrier. Clopidogrel proniosomes were evaluated for their entrapment efficiency and in vitro drug release. The best formula (F1) that achieved maximum drug release was further evaluated by measurement of the angle of repose, morphological examination, determination of vesicle size, determination of zeta potential, Fourier transform infrared spectroscopy and differential thermal analysis. The in vivo behavior of the selected proniosomal formula (F1) was studied by measuring the antiplatelet activity in adult male mice. Results:The entrapment efficiency of clopidogrel proniosomes was in the range of 83.04±1.99 to 90.14±0.30. % drug released from proniosomal formulations was in the range of 79.73±0.35 to 97.70±1.10 % within 4 h. Clopidogrel proniosomes significantly enhanced the in vitro release of clopidogrel compared with the plain drug that achieved 61.77±2.22 % drug release. F1 significantly (p ≤ 0.001) increased the bleeding time and bleeding volume and significantly (p ≤ 0.05) prolonged prothrombin time and decreased prothrombin activity and increased the international normalized ratio (INR) compared to plain clopidogrel. Conclusion:The present investigation introduced proniosomes as a promising carrier for clopidogrel that could enhance its dissolution and pharmacological effect. I In nt te er rn na at ti io on na al l J Jo ou ur rn na al l o of f A Ap pp pl li ie ed d P Ph ha ar rm ma ac ce eu ut ti ic cs s

Objective To enhance bioavailability of timolol (TML) and utilize alternatives for traditional eye drops for more patient compliance, this study was aiming to develop biodegradable orally dissolving strips (ODSs) of TML for treatment of primary open‐angle glaucoma (POAG). Methods Novel ODSs of TML were formulated and optimized using solvent casting method according to full factorial design (31.22). TML ODSs were characterized with respect to many parameters. In‐vivo test was carried out using four groups of 24 New Zealand albino rabbits. POAG was induced by subconjunctival treatment of betamethasone. Histopathological examination and oxidative stress markers assay were carried out. Key findings The optimized formula (F9) exhibited a remarkably 15‐s disintegration time and 96% dissolution rate after 10 min. The results revealed a potent significant inhibitory effect of the optimized TML ODS to reduce IOP in induced rabbits in comparison with control rabbits and TML eye drops‐treated rabbits. The formula showed also high activity against oxidative stress and absence of histopathological changes in iridocorneal angle and cornea. Conclusion The ODSs could be a promising alternative delivery system for eye drops with more compliance to enhance delivery and therapeutic activity of TML in treatment of POAG.

Background: To compare intravenous labetalol with oral nifedipine in terms of rapidity at which they control blood pressure in acute hypertensive emergencies of pregnancy.Methods: A randomized controlled study. Pregnant women with severe gestational hypertension with BP ≥160/110 mmHg after ≥20 weeks of gestation were randomized with computer generated numbers, either to receive IV labetalol with an escalating dose of 20, 40, 80, 80 and 80 mg or nifedipine capsule orally in a dose of 10 mg every 15 minutes (upto 5 doses) until a BP of ≤150/100 mmHg is achieved. Crossover treatment was to be effected if initial treatment regimen was unsuccessful. Primary outcome was time taken and number of doses required to achieve the target BP of ≤150/100 mmHg. Secondary outcomes were volume of urine output, maternal heart rate changes, fetal heart rate abnormality, perinatal and maternal outcome and side effects.Results: Oral nifedipine achieved the target BP (≤150/100 mmHg) more rapidly in (26.25±12.60) minutes in comparison to (32.62±12.19) minutes with IV labetalol (p= 0.024). Nifedipine group also took less number of doses to achieve the target BP of (≤150/100 mmHg) mmHg than IV labetalol (1.75±0.840 vs. 2.18±0.83), p= 0.024. Volume of urine output was also significantly more in nifedipine group (94.90±1.84 ml) at 1 hour and thereafter till 24 hour of treatment in comparison to IV labetalol (41.28±2.14 ml), p= 0.000. Side effects are few and not serious. No patient required crossover treatment.Conclusions: Both the drugs are equally effective in controlling acute hypertensive emergencies of pregnancy, however oral nifedipine is more rapid in controlling severe hypertension and also it is associated with significantly increased urine output.

Prostaglandin E 2 (PGE 2 ) is a potent physiological suppressor of liver fibrosis. Because the anti-ulcer drug rebamipide can induce the formation of endogenous PGE 2 , this study investigated the potential effects of rebamipide on development of a hepatic fibrosis that was inducible by carbon tetrachloride (CCl 4 ). Groups of Wistar rats received intraperitoneal (IP) injections of CCl 4 (0.45 ml/kg [0.72 g CCl 4 /kg]) over the course of for 4 weeks. Sub-sets of CCl 4 -treated rats were also treated concurrently with rebamipide at 60 or 100 mg/kg. At 24 h after the final treatments, liver function and oxidative stress were indirectly assessed. The extent of hepatic fibrosis was evaluated using two fibrotic markers, hyaluronic acid (HA) and pro-collagen-III (Procol-III); isolated liver tissues underwent histology and were evaluated for interleukin (IL)-10 and PGE 2 content. The results indicated that treatment with rebamipide significantly inhibited CCl 4 -induced increases in serum ALT and AST and also reduced oxidative stress induced by CCl 4 . Fibrotic marker assays revealed that either dose of rebamipide decreased the host levels of Procol-III and HA that had become elevated due to the CCl 4 . At the higher dose tested, rebamipide appeared to be able to permit the hosts to have a normal liver histology and to minimize any CCl 4 -induced collagen precipitation in the liver. Lastly, the use of rebamipide was seen to be associated with significant increases in liver levels of both PGE 2 and the anti-inflammatory cytokine IL-10. Based on these findings, it is concluded that rebamipide can retard hepatic fibrosis induced by CCl 4 and that this effect may, in part, be mediated by an induction of PGE 2 and IL-10 in the liver itself. ARTICLE HISTORY