Optimization of Lovastatin Self-Nanoemulsifying Solid Dosage Form

ACKNOWLEDGEMENTS: I am very thankful to Dr Sanjay S. Patel for his great support for this research work. We are also thankful to Manager of Abitech Corporation, USA, Corel Chemical Ltd., Ahmedabad, and Torrent Pharmaceuticals Ltd., Ahmedabad for providing us necessary ingredients. We are thankful to Shri B. M. Shah College of Pharmaceutical Education and Research, Modasa for providing technical support in form of instruments and guidance.Aim: The aim of present study was to develop and optimized self-nanoemulsifying solid dosage form (SNESDF) of Lovastatin for enhancing its solubility. Lovastatin (whose water solubility is 0.4 x 10-3 mg/mL) is considered to be a reasonable drug because of its high log P value (4.3) and good solubility in oils. Materials and Methods: The formulations were optimized by Box-Behnken statistical design in which the independent variables like Ratio of surfactant: co-surfactant (X1), oil: surfactant co surfactant (X2), and % Aerosil (X3). The formulations were characterized for its dependent variables such as Droplet size (Y1), transmittance (Y3), percentage of drug released within 5 minutes (Y3), and within 15 minutes (Y4). Results and Conclusion: Droplet size and zeta potential of the optimized batch was found to be 21.89 nm and -6.4 mV, respectively. 44.32 % and 90.78 % of the drug was found to be released within 5 min and 15 min, respectively. Hence, by formulating into SNESDF, the solubility of Lovastatin was found to be significantly improved.Objetivo: El objetivo del presente estudio fue desarrollar y optimizar la auto-nanoemulsión forma de dosificación sólida (SNESDF) de la Lovastatina para aumentar su solubilidad. Lovastatina (cuya solubilidad en agua es 0,4 x 10-3 mg / ml) se considera que es un fármaco razonable debido a su alto valor de log P (4,3) y una buena solubilidad en aceites. Materiales y Métodos: Las formulaciones fueron optimizadas por el diseño estadístico Box-Behnken en el cual las variables independientes como relación de tensioactivo: tensioactivo co-(X1), aceite: tensioactivo co tensioactivo (X2), y% Aerosil (X3). Las formulaciones se caracterizan por sus variables dependientes, tales como tamaño de la gota (Y1), la transmitancia (Y3), el porcentaje de fármaco liberado en 5 minutos (Y3), y dentro de 15 minutos (Y4). Resultados y Conclusiones: tamaño de la gota y el potencial zeta del lote optimizado resultó ser 21,89 nm y -6,4 mV, respectivamente. 44,32% y 90,78% del fármaco se encontró que se libera dentro de 5 min y 15 min, respectivamente. Por lo tanto, mediante la formulación en SNESDF de lovastatina , se encontró que la solubilidad mejoraba significativamente

A Failure Analysis and Remaining Life assessment of Boiler Water Wall tube

This paper presents failure investigation on the SA210GrC water wall tube by visual Site inspection, tube wall thickness measurements, chemical composition test, Hardness test and microstructure analysis with proper evidence collected to identify the exact cause of the failure. The water wall tube was failed with blister, bulging and creep cracks on outer surface located near to the Soot Blower. On-site wall thickness measurements were performed on some of the water wall tubes located at the same level of the ruptured tube. The tubes have significant wall thinning and erosion from outside. Mild corrosion deposition also seen in the inner side. Microscopic examinations on the failed rupture region and some distance away of the as-received tubes are also conducted in order to determine the failure mechanism and root cause. Failure mechanisms are also discussed and relevant data from few months back to the failure gathered to identify the failure reason. The failure mechanism is identified as a result of the combination of the significant wall thinning of water wall tube due to long term overheating and creep. Corrosion due to oxygen is also a cause of wall thinning. Root cause analysis identified that deaerator was not working efficient to remove dissolved gases was reason behind corrosion. Long term overheating was due to operating temperature above the design one. Finally all the parameters checked and rectified properly. Maintenance of Deaerator has been done to put it in the working condition

Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation

Inflammasome activation, with subsequent release of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, has recently been implicated in atherosclerosis-associated inflammation. This study aims to assess in acute coronary syndrome (ACS) patients (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation. ACS patients (n=21) were randomized to oral colchicine (1 mg followed by 0.5 mg 1 h later) or no treatment, and compared with untreated healthy controls (n=9). Peripheral venous blood was sampled pre- (day 1) and 24 h post- (day 2) treatment. Monocytes were cultured and stimulated with ATP. Analysis of key inflammasome markers was performed by ELISA. IL-1β secretion increased by 580.4% (P<0.01) in ACS patients compared with controls but only with ATP stimulation. Untreated ACS patients secreted significantly higher levels of IL-18 compared with healthy controls independent of ATP stimulation (P<0.05). Colchicine treatment in ACS patients markedly reduced intracellular and secreted levels of IL-1β compared with pre-treatment levels (P<0.05 for both), as well as significantly reducing pro-caspase-1 mRNA levels by 57.7% and secreted caspase-1 protein levels by 30.2% compared with untreated patients (P<0.05 for both). Monocytes from ACS patients are ‘primed’ to secrete inflammasome-related cytokines and short-term colchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing monocyte secretion of IL-1β

Sadašnjost i budućnost stentova za restenozu koji otpuštaju lijekove

Drug-eluting stents (DESs) prevail in the treatment of carotid artery diseases in the interventional cardiology world owing to their efficacy for significant reduction of restenosis. A current successful DES requires a polymer coating for drug delivery. Clinical trials examining several pharmaceutical agents have demonstrated marked reduction in restenosis following stenting. The development of DES is one of the major revolutions in the field of interventional cardiology. The ideal drug to prevent restenosis must have an anti-proliferative and anti-migratory effect on smooth muscle cells but, on the other hand, it must also enhance re-endothelialization in order to prevent late thrombosis. Additionally, it should effectively inhibit the anti-inflammatory response after balloon induced arterial injury. Although DES have significantly reduced the angiographic restenosis rate and have improved clinical outcomes, late thrombosis and restenosis remain an important subject of ongoing research.Stentovi koji otpuštaju lijekove (DESs) koriste se u kardiologiji za terapiju bolesti karotidnih arterija jer značajno smanjuju restenozu. Dobar DES ima polimerni sloj za isporuku lijekova. Klinički pokusi u kojima je ispitivano nekoliko agenasa pokazali su značajno smanjenje restenoze nakon ugradnje stenta. Razvoj DES-a jedno je od revolucionarnih otkrića u području interventne kardiologije. Idealni lijek za prevenciju restenoze mora imati antiproliferativni i antimigracijski učinak na stanice glatkih mišića, a s druge strane mora povećavati endotelizaciju kako bi se spriječila tromboza. Osim toga, treba učinkovito inhibirati protuupalni odgovor nakon ozljede arterije. Iako DES značajno smanjuje restenozu krvnih žila, kasna tromboza i restenoza ostaju i dalje problem i predmet brojnih istraživanja

High speed all-optical switching based on a single-arm interferometer

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1996.Includes bibliographical references (leaves 125-133).by Naimish S. Patel.M.Eng

Sleep Disturbances and Glucose Metabolism in Older Adults: The Cardiovascular Health Study.

ObjectiveWe examined the associations of symptoms of sleep-disordered breathing (SDB), which was defined as loud snoring, stopping breathing for a while during sleep, and daytime sleepiness, and insomnia with glucose metabolism and incident type 2 diabetes in older adults.Research design and methodsBetween 1989 and 1993, the Cardiovascular Health Study recruited 5,888 participants ≥65 years of age from four U.S. communities. Participants reported SDB and insomnia symptoms yearly through 1989-1994. In 1989-1990, participants underwent an oral glucose tolerance test, from which insulin secretion and insulin sensitivity were estimated. Fasting glucose levels were measured in 1989-1990 and again in 1992-1993, 1994-1995, 1996-1997, and 1998-1999, and medication use was ascertained yearly. We determined the cross-sectional associations of sleep symptoms with fasting glucose levels, 2-h glucose levels, insulin sensitivity, and insulin secretion using generalized estimated equations and linear regression models. We determined the associations of updated and averaged sleep symptoms with incident diabetes in Cox proportional hazards models. We adjusted for sociodemographics, lifestyle factors, and medical history.ResultsObserved apnea, snoring, and daytime sleepiness were associated with higher fasting glucose levels, higher 2-h glucose levels, lower insulin sensitivity, and higher insulin secretion. The risk of the development of type 2 diabetes was positively associated with observed apnea (hazard ratio [HR] 1.84 [95% CI 1.19-2.86]), snoring (HR 1.27 [95% CI 0.95-1.71]), and daytime sleepiness (HR 1.54 [95% CI 1.13-2.12]). In contrast, we did not find consistent associations between insomnia symptoms and glucose metabolism or incident type 2 diabetes.ConclusionsEasily collected symptoms of SDB are strongly associated with insulin resistance and the incidence of type 2 diabetes in older adults. Monitoring glucose metabolism in such patients may prove useful in identifying candidates for lifestyle or pharmacological therapy. Further studies are needed to determine whether insomnia symptoms affect the risk of diabetes in younger adults

Neutrophil-derived microparticles are released into the coronary circulation following percutaneous coronary intervention in acute coronary syndrome patients.

To evaluate (i) local coronary and systemic levels of microparticles (MP) in acute coronary syndrome (ACS) and stable angina pectoris (SAP) patients and (ii) their release after plaque disruption with percutaneous coronary intervention (PCI). MP are small vesicles originating from plasma membranes of cells after activation or apoptosis and are implicated in the pathogenesis of atherosclerosis. Neutrophils play a role in plaque destabilization and shed neutrophil-derived MP that have the potential to drive significant proinflammatory and thrombotic downstream effects. Eight ACS and eight SAP patients were included. Coronary sinus (CS) samples pre-intervention (CS1), 45 s following balloon angioplasty (CS2) and at 45 s intervals following stent deployment (CS3, CS4 and CS5), together with peripheral vein samples, pre- and post-PCI were analysed for neutrophil-derived (CD66b+), endothelial-derived (CD144+), platelet-derived (CD41a+), monocyte-derived (CD14+) and apoptotic (Annexin V+) MP. ELISA for interleukin (IL)-6, myeloperoxidase (MPO) and P-selectin was also performed. CD66b+ MP levels were similar in both groups pre-intervention. Post-PCI, CS levels rose significantly in ACS but not SAP patients (ACS area under the curve (AUC): 549 ± 83, SAP AUC: 24 ± 29, P<0.01). CS CD41a+, CD144+, CD14+ and Annexin V+ MP levels did not differ between groups. Acute neutrophil-derived MP release post-PCI occurs in ACS compared with stable patients, likely to be reflective of plaque MP content in vulnerable lesions