In vitro evaluation and in vivo performance of lyophilized gliclazide

Enhancement of the dissolution rate of the poorly water-soluble hypoglycemic agent, gliclazide, by the aid of lyophilization was investigated. Mannitol, sodium lauryl sulfate (SLS) and polyvinyl pyrrolidone (PVP-k-30) were employed in different weight ratios (43%, 56% and 64% w/w, respectively) as water-soluble excipients in the formulation. Lyophilized systems were found to exhibit extremely higher in vitro dissolution rate compared to the unprocessed drug powder. Solid state characterization of the lyophilized systems using X-ray powder diffraction, Fourier transform infrared spectroscopy and differential scanning calorimetry techniques revealed that dissolution enhancement was attributable to transformation of gliclazide from the crystalline to an amorphous state in the solid dispersion formed during the lyophilization process. The gastrointestinal absorption and hypoglycemic effect of the lyophilized gliclazide/SLS system were investigated following oral administration to Albino rabbits. C_max and area under the plasma concentration–time curve of gliclazide (AUC_0–12) after administration of the lyophilized formulations were significantly higher than those obtained after administration of the unprocessed gliclazide.     

Formulation and in vitro Evaluation of pH-Sensitive Cross-linked Xanthan Gum-Grafted Acrylic Acid Copolymer for Controlled Delivery of Perindopril Erbumine (PE)

A novel xanthan gum-co-acrylic acid superabsorbent hydrogel composite was formulated by free radical polymerization reaction of acrylic acid on xanthan gum. Effect of variables like dynamic swelling ratio, equilibrium swelling ratio, drug loading and drug release was investigated. Swelling ratio increases with decrease in crosslinker concentration. Drug release studies were conducted in pH 7.4 and 0.1N HCl. In acidic environment, drug release was low whereas it was sustained release in alkaline. XG4 showed significant swelling and drug release up to 24?hr. Physicochemical evaluation also confirmed it was optimized formulation. Hence XG4-co-AA was optimized for once daily dose of Perindopril Erbumine.     

GABA and glutamate levels in the substantia nigra reticulata following repetitive cerebral ischemia in gerbils

Repetitive cerebral ischemia produces more severe damage than a similar single duration insult. We have previously shown that, in gerbils, damage in the substantia nigra reticulata (SNr) is seen with repetitive insults rather than a single insult. We have also shown that there is a progressive decrease in the extracellular GABA in the striatum in the days preceding such damage, speculating that a loss of GABA may be in part responsible for this damage. This study evaluates the GABA levels in the SNr in animals exposed to repetitive ischemic insults. Each animal received a total of three ischemic insults of 3-min duration at hourly intervals. In vivo microdialysis was carried out to analyze the GABA and glutamate dialysate levels on Days 1, 3, 5, 7, and 14 following the ischemic insult. In the control and treated (ischemic) animals, there was a significant increase in the GABA levels with the introduction of nipecotic acid on Days 1, 3, 5, and 14. However, on Day 7 there was a significant attenuation in the GABA response to nipecotic acid in the treated animals in comparison to the controls. The glutamate levels in the treated animals were similar to the control animals on Days 1, 3, 5, and 7. However, on Day 14 the glutamate levels were significantly lower than on previous days. Our experiments for the first time measure extracellular glutamate and GABA responses in the SNr in animals exposed to repetitive ischemic insults. Our experiments show that there is a significant decrease in the GABA concentrations at a time when ischemic damage is developing in this region. This confirms our hypothesis that a decrease in GABA may be one factor contributing to neuronal damage during the period following repetitive ischemic insults. Further, the rebound increase in GABA levels on Day 14 with a concomitant fall in glutamate levels would indicate that reparative processes are still active in the 2 weeks following the insult.     

Thrombolytic therapy for unstable angina

Thrombolytic therapy for unstable angina has not gained acceptance as a primary treatment for unstable angina (UA) despite the evidence showing a reduction in mortality when these agents are given for myocardial infarction. The purpose of this review is to examine the clinical value of thrombolytic therapy for UA. The multiple lines of evidence supporting intracoronary thrombus formation as a key mechanism in the pathogenesis of UA are reviewed. Studies examining the effect of thrombolytic therapy on angiographic endpoints have shown little effect on the extent of luminal narrowing, but do reveal a decrease in angiographically detected thrombus. Twelve randomized, controlled trials of thrombolytic agents in 611 UA patients with predefined clinical endpoints have been published. These trials varied widely in design and adjunctive therapy both in treated and control grops. Review of these trials show a tendency to fewer clinical events such as death, infarction, and need for revascularization in treated patients, with a corresponding increase in bleeding complications. Clinical efficacy of thrombolytic therapy cannot be excluded by the available data, perhaps in part because of insufficient numbers of patients treated. Determination of the net clinical value of thrombolytic therapy must await larger and more definitive trials.     

Synthesis and thermomechanical characterization of polyurethane elastomers extended with α,ω‐alkane diols

A series of polyurethane (PU) elastomers was prepared by the reaction of poly(?‐caprolactone) and 4,4′‐diphenylmethane diisocyanate, which was extended with a series of chain extenders (CEs) having 2–10 methylene units in their structure. The completion of the reaction was confirmed by Fourier transform infrared spectroscopy. The chemical structures of the synthesized PU samples were characterized with Fourier transform infrared, ¹H‐NMR, and ¹³C‐NMR spectroscopy, and the thermal properties were determined by thermogravimetric analysis, DSC, and dynamic mechanical thermal analysis techniques. The mechanical properties were also studied and are discussed. The thermogravimetric analysis and DSC analysis showed that CE length had a considerable effect on the thermal properties of the prepared samples. The dynamic mechanical thermal analysis and damping peaks were also affected by the number of methylene units in the CE length. The elastomer extended with 1,2‐ethane diol exhibited optimum thermal properties, whereas the elastomer based on 1,10‐decane diol displayed the worst thermal properties. Tensile strength and elongation at break decreased with increasing CE length, whereas hardness showed the opposite trend. The glass‐transition temperature moved toward lower temperatures with increasing CE length. The decrease in the glass‐transition temperature and tensile properties were interpreted in terms of decreasing hard segments and increasing chain flexibility. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

A hybrid model for spelling error detection and correction for Urdu language

Neural Computing and Applications - Detecting and correcting misspelled words in a written text are of great importance in many natural language processing applications. Errors can be broadly...     

Effect of green manure on the yield,N uptake and floodwater properties of a flooded rice,wheat rotation receiving15N urea on a highly permeable soil

Field studies were conducted for two years on a rapidly percolating loamy sand (Typic Ustochrept) to evaluate the effect of green manure (GM) on the yield,¹⁵N recovery from urea applied to flooded rice, the potential for ammonia loss and uptake of residual fertilizer N by succeeding crops. The GM crop ofSesbania aculeata was grownin situ and incorporated one day before transplanting rice. Urea was broadcast in 0.05 m deep floodwater, and incorporated with a harrow. Green manure significantly increased the yield and N uptake by rice and substituted for a minimum of 60 kg fertilizer N ha^–1. The recovery of fertilizer N as indicated by¹⁵N recovery was higher in the GM + urea treatments. The grain yield and N uptake by succeeding wheat in the rotation was slightly higher with GM. The recovery of residual fertilizer N as indicated by the¹⁵N recovery in the second, third and fourth crops of wheat, rice and wheat was only 3, 1 and 1 per cent of the urea fertilizer applied to the preceding rice crop. Floodwater chemistry parameters showed that the combined use of the GM and 40 kg N ha^–1 as urea applied at transplanting resulted in a comparatively higher potential for NH₃ loss immediately after fertilizer application. The actual ammonia loss as suggested by the¹⁵N recoveries in the rice crop, however, did not appear to be appreciably larger in the GM treatment. It appeared the ammonia loss was restricted by low ammoniacal-N concentration maintained in the floodwater after 2 to 3 days of fertilizer application.