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Three-dimensional aspects of formulation excipients in drug discovery:a critical assessment on orphan excipients,matrix effects and drug interactions

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Journal of Pharmaceutical Analysis 2020年第6期10卷 522-531页

作者： Vijayabhaskar Veeravalli Hanumanth srikanth Cheruvu Pratima Srivastava Lakshmi Mohan Vamsi Madgula Syngene International Limited Biocon ParkSEZBommasandra Industrial Area-Phase-IV Bommasandra-Jigani Link RoadBangalore560099India GVK BIO Pvt Ltd NacharamHyderabadTelangana500076India

Formulation/pharmaceutical excipients play a major role in formulating drug candidates,with the objectives of ease of administration,targeted delivery and complete *** excipients used in pharmaceutical formulations are orphanized in preclinical drug *** orphan excipients could enhance formulatability of highly lipophilic ***,they are safe in preclinical species when used below the LD50 ***,when the excipients are used in formulating compounds with diverse physico-chemical properties,they pose challenges by modulating study results through their bioanalytical matrix *** invariably present in study samples and not in the calibration curve standards cause over-/under-estimation of ***,the mechanism by which excipients cause matrix effects and strategies to nullify these effects needs to be ***,formulation excipients cause drug interactions by moderating the pathways of drug metabolizing enzymes and drug transport *** it is not possible to get rid of excipient driven interactions,it is always advised to be aware of these interactions and apply the knowledge to draw meaningful conclusions from study *** this review,we will comprehensively discuss a)orphan excipients that have wider applications in preclinical formulations,b)bioanalytical matrix effects and possible approaches to mitigating these effects,and c)excipient driven drug interactions and strategies to alleviate the impacts of drug interactions.

关键词： Formulation excipients Preclinical Drug discovery Matrix effects Drug interactions Bioanalysis Pharmacokinetics Formulation development

Experimental and computational investigations on the SO_(2) poisoning of(La_(0.8)Sr_(0.2))_(0.95)MnO_(3) cathode materials

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Advanced Powder Materials

Advanced Powder Materials 2023年第1期2卷 25-34页

作者： Rui Wang Lucas R.Parent srikanth Gopalan Yu Zhong Mechanical and Materials Engineering Department Worcester Polytechnic InstituteWorcesterMA 01609USA Innovation Partnership Building University of ConnecticutStorrsCT 06269USA Division of Materials Science&Engineering Boston UniversityBostonMA 02215USA

To study the formation of detrimental phases under the sulfur gas impurity to the long-term degradation in the cathode material,the classic cathode material,(La_(0.8)Sr_(0.2))_(0.95)MnO_(3)(LSM),was prepared,sintered,and annealed at 800,900,and 1000℃ in the sulfur-containing atmospheres,*** X-ray diffraction,scanning electron microscope,and transmission electron microscopy techniques,as well as the computer coupling of phase diagrams and thermochemistry methodology,the secondary phases,especially the detrimental ones,under different conditions were predicted and experimentally verified ***,sulfur poisoning results indicate that the accelerated tests might have degradation mechanisms different from actual operation *** importantly,comprehensive comparisons among various impurity-containing conditions were also made to recommend better operation parameters.

关键词： LSM cathode CALPHAD Sulfur poisoning Long-term degradation Accelerated test

Potential drug–drug interactions in pediatric wards of Gondar University Hospital,Ethiopia:A cross sectional study

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Asian Pacific Journal of Tropical Biomedicine 2016年第6期6卷 534-538页

作者： Henok Getachew Mohammed Assen Feser Dula Akshaya srikanth Bhagavathula Department of Clinical Pharmacy School of PharmacyCollege of Medical and Health ScienceUniversity of Gondar Department of Hospital Pharmacy Drug Information Center and Clinical Pharmacy UnitGondar University Hospital

Objective: To determine the prevalence, level of severity of potential drug–drug interactions(PDDIs) and the associated factors for PDDIs in hospitalized pediatric patients of Gondar University ***: A retrospective cross-sectional study was conducted for a period of 3 months from March to May 2014 in pediatric wards of Gondar University Hospital. Systematic random sampling technique was used to select charts from all pediatric patients' charts with every 7th interval to get sample size of 384. Univariate and multivariate analysis were performed to compute crude odds ratio and adjusted odds ratio respectively. Statistical significance was set at P value < ***: A total of 176(45.8%) patients had at least one PDDI. A total of 393 PDDIs,which were comprised of 283 types of interacting combinations, were identified. Of the total of 393 PDDIs, most were of moderate severity [201(51%)] followed by minor [152(39%)] and major severity [40(10%)]. The most common interacting pairs of major severity were gentamicin + furosemide(6), cotrimoxazole + methotrexate(4) and phenytoin + artemether(4). The occurrence of PDDIs was significantly associated with age and ***: The study showed that most of the interactions had moderate severity followed by minor severity. Age and polypharmacy were found to show statistically significant association with the occurrence of PDDIs. Due to sensitive nature of pediatrics population, close monitoring is recommended for the detection and management of PDDIs to prevent its negative consequences.

关键词： Potential drug–drug interaction Pediatric ward Prevalence Ethiopia

Mathematical modelling of couple stresses on fluid flow in constricted tapered artery in presence of slip velocity-effects of catheter

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Applied Mathematics and Mechanics(English Edition) 2014年第8期35卷 947-958页

作者： J.V.R.REDDY D.srikanth S.K.MURTHY Department of Applied Mathematics Defence Institute of Advanced Technology Deemed UniversityPune 411025MaharastraIndia

This paper explores the mathematical model for couple stress fluid flow through an annular region. The above model is used for studying the blood flow be-tween the clogged （stenotic） artery and the catheter. The asymmetric nature of the stenosis is considered. The closed form expressions for the physiological parameters such as impedance and shear stress at the wall are obtained. The effects of various geomet-ric parameters and the parameters arising out of the fluid considered are discussed by considering the slip velocity and tapering angle. The study of the above model is very significant as it has direct applications in the treatment of cardiovascular diseases.

关键词： blood flow couple stress fluid stenosed artery tapered artery catheter

Distributed resource scheduling in smart grid with electric vehicle deployment using fireworks algorithm

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Journal of Modern Power Systems and Clean Energy 2016年第2期4卷 188-199页

作者： K.srikanth REDDY Lokesh Kumar PANWAR Rajesh KUMAR Bijaya Ketan PANIGRAHI IIT Delhi New DelhiIndia MNIT Jaipur JaipurRajasthanIndia

Global warming and climate change are two key probing issues in the present *** electricity sector and transportation sector are two principle entities propelling both these *** from these two sectors can be offset by switching to greener ways of transportation through the electric vehicle (EV) and renewable energy technologies (RET).Thus,effective scheduling of both resources holds the key to sustainable *** paper presents a scheduling scenario-based approach in the smart *** formulation with dual objective function including both emissions and cost is developed for conventional unit commitment with EV and RET *** this work,the scheduling and commitment problem is solved using the fireworks algorithm which mimics explosion of fireworks in the sky to define search space and the distance between associated sparks to evaluate global ***,binary coded fireworks algorithm is developed for the proposed scheduling problem in the smart ***,possible scenarios inconventional as well as smart grid are put *** that,the proposed methodology is simulated using a test system with thermal generators.

关键词： Unit commitment problem(UCP) Binary fireworks algorithm(BFWA) Constrained optimization Renewable energy technologies(RETs) Plug-in electric vehicle(PEV)

Supergranular Fractal Dimension and Solar Rotation

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Research in Astronomy and Astrophysics 2022年第9期22卷 239-244页

作者： G.M.Sowmya G.Rajani U.Paniveni R.srikanth GSSS Institute of Engineering and Technology for Women Mysuru-570016KarmatakaIndia PES College of Engineering Mandya-571401KarnatakaIndia Bangalore University JnanabharathiBengaluru-560056India Poornaprajna Institute of Scientific Research DevanahalliBangalore-562110KamatakaIndia

We present findings from an analysis of the fractal dimension of solar supergranulation as a function of latitude,supergranular cell size and solar rotation, employing spectroheliographic data in the Ca II K line of solar cycle no.23. We find that the fractal dimension tends to decrease from about 1.37 at the equator to about 1 at 20° latitude in either hemisphere, suggesting that solar rotation rate has the effect of augmenting the irregularity of supergranular boundaries. Considering that supergranular cell size is directly correlated with fractal dimension, we conclude that the mechanism behind our observation is that solar rotation influences the cell outflow strength, and thereby cell size, with the latitude dependence of the supergranular fractal dimension being a consequence thereof.

关键词： Sun:chromosphere Sun:rotation Sun:magnetic fields

Treatment of gastrointestinal bleeding in left ventricular assist devices:A comprehensive review

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World Journal of Gastroenterology 2020年第20期26卷 2550-2558页

作者： srikanth Vedachalam Gokulakrishnan Balasubramanian Garrie J Haas Somashekar G Krishna Department of Internal Medicine The Ohio State University Wexner Medical CenterColumbusOH 43210United States Division of Gastroenterology Hepatology and NutritionThe Ohio State University Wexner Medical CenterColumbusOH 43210United States Division of Cardiovascular Medicine The Ohio State University Wexner Medical CenterColumbusOH 43210United States

Left ventricular assist devices(LVAD)are increasingly become common as life prolonging therapy in patients with advanced heart *** devices are now used as definitive treatment in some patients given the improved durability of continuous flow ***,continuous flow LVADs are fraught with complications such as gastrointestinal(GI)bleeding that are primarily attributed to the formation of arteriovenous *** frequent GI bleeding,antiplatelet and anticoagulation therapies are usually discontinued increasing the risk of life-threatening *** bowel bleeds account for 15%as the source and patients often undergo multiple endoscopic *** strategies include resuscitative measures and endoscopic *** treatment is with *** treatment options include thalidomide,angiotensin converting enzyme inhibitors/angiotensinⅡreceptor blockers,estrogen-based hormonal therapies,doxycycline,desmopressin and *** research has explored the mechanism of frequent GI bleeds in this population,including destruction of von Willebrand factor,upregulation of tissue factor,vascular endothelial growth factor,tumor necrosis factor-α,tumor growth factor-β,and angiopoetin-2,and downregulation of *** addition,healthcare resource utilization is only increasing in this patient population with higher admissions,readmissions,blood product utilization,and *** some of the novel endoscopic and medical therapies for LVAD bleeds are still in their development stages,these tools will yet be crucial as the number of LVAD placements will likely only increase in the coming years.

关键词： Left ventricular assist device Push enteroscopy Double balloon enteroscopy Video capsule endoscopy Octreotide Bevacizumab Gastrointestinal bleeding

Solar Supergranular Fractal Dimension Dependence on the Solar Cycle Phase

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Research in Astronomy and Astrophysics 2022年第4期22卷 55-61页

作者： G.Rajani G.M.Sowmya U.Paniveni R.srikanth PES College of Engineering Mandya-571401KarnatakaIndia GSSS Institute of Engineering and Technology for Women KRS RoadMetagalli Mysuru-570016KarnatakaIndia Bangalore University JnanabharathiBengaluru-560056India Poornaprajna Institute of Scientific Research DevanahalliBangalore-562110KarnatakaIndia

We study the complexity of the supergranular network through fractal dimension by using the Ca II K digitized data archive obtained from the Kodaikanal Solar *** data consist of 326 visually selected supergranular cells spread across the 23rd solar *** cells that were well-defined were chosen for the analysis and we discuss the potential selection effect thereof,mainly that it favors cells of a smaller size(<20 Mm).Within this sample,we analyzed the fractal dimension of supergranules across the solar cycle and find that it is anticorrelated with the activity level.

关键词： Sun:chromosphere Sun:granulation Sun:activity

Stormwater treatment： examples of computational fluid dynamics modeling

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Frontiers of Environmental Science & Engineering 2012年第5期6卷 638-648页

作者： Gaoxiang YING John SANSALONE srikanth PATHAPATI Giuseppina GAROFALO Marco MAGLIONICO Andrea BOLOGNESI Alessandro ARTINA Engineering School of Sustainable Infrastructure and Environment University of Florida Gainesville FL 32611-6450 USA DISTART Universita di Bologna Viale del Risorgimento 2 40136 Bologna Italia

Control of rainfall-runoff particulate matter （PM） and PM-bound chemical loads is challenging; in part due to the wide gradation of PM complex geometries of many unit operations and variable flow rates. Such challenges and the expense associated with resolving such challenges have led to the relatively common examination of a spectrum of unit operations and processes. This study applies the principles of computa- tional fluid dynamics （CFD） to predict the particle and pollutant clarification behavior of these systems subject to dilute multiphase flows, typical of rainfall-runoff, within computationally reasonable limits, to a scientifically acceptable degree of accuracy. The Navier-Stokes （NS） system of nonlinear partial differential equations for multi- phase hydrodynamics and separation of entrained particles are solved numerically over the unit operation control volume with the boundary and initial conditions defined and then solved numerically until the desired convergence criteria are met. Flow rates examined are scaled based on sizing of common unit operations such as hydrodynamic separators （HS）, wet basins, or filters, and are examined from 1 to 100 percent of the system maximum hydraulic operating flow rate. A standard turbulence model is used to resolve flow, and a discrete phase model （DPM） is utilized to examine the particle clarification response. CFD results closely follow physical model results across the entire range of flow rates. Post-processing the CFD predictions provides an in-depth insight into the mechanistic behavior of unit operations by means of three dimensional （3-D） hydraulic profiles and particle trajectories. Results demon- strate the role of scour in the rapid degradation of unit operations that are not maintained. Comparisons are provided between measured and CFD modeled results and a mass balance error is identified. CFD is arguably the most powerful tool available for our profession since continuous simulation modeling.

关键词： stormwater unit operations and processes(UOPs) hydrodynamic separation filtration adsorption,computational fluid dynamics (CFD) turbulence modeling,discrete phase model particle separation detention/reten-tion basins clarification