Generic placeholder image

Current Nanomedicine

Editor-in-Chief

ISSN (Print): 2468-1873
ISSN (Online): 2468-1881

Research Article

DoE Enabled Development and In-Vitro Optimization of Curcumin-tagged Cilostazol Solid Nano Dispersion

Author(s): Aruna Rawat, Vikas Jhawat* and Rohit Dutt

Volume 13, Issue 2, 2023

Published on: 15 August, 2023

Page: [113 - 131] Pages: 19

DOI: 10.2174/2468187313666230719121457

Abstract

Background: Diabetes is a prevailing disease worldwide and its complications are also hazardous including nephropathy. Drug available to treat Diabetic Nephropathy (DN) faces bioavailability issues related to solubility and absorption of drugs. Cilostazol (CLT) is a BCS class II drug that is poorly water-soluble which affects its therapeutic efficacy. CLT reduces reactive oxygen species (ROS) increased in DN. Curcumin (Cur) is also hydrophobic but Cur has many therapeutic efficacies like anti-inflammatory and antioxidant properties that help for the treatment of DN.

Objective: The objective of the current study was to develop and optimize the Cilostazol Solid Dispersion Nanoparticle (SDN) to improve the bioavailability of the drug by tagging it with Cur by using PVP VA S 630 as polymer and Poloxamer 407 as surfactant.

Method: Different formulations were developed using the emulsion solvent evaporation method, PVP VA S 630 as the hydrophilic polymer, and Poloxamer 407 as a surfactant. Two-factor, threelevel Box-Behnken Design (BBD) was used for statistical analysis of the selected process variable's main effect and interactive effect on the response. Curcumin tagging was also done for the entire batches. Nanoparticles were characterized by FT-IR spectroscopy, DSC, Particle size, Zeta potential, Drug entrapment efficiency, Solubility, and % CDR studies.

Results: Among the 17 different formulations (CLT1-CLT 17), with a solubility of 39.5 μg/ml, a % CDR of 99.55, a typical particle size of 219.67 nm with a PDI of 0.258, entrapment efficiency of 73.47%, and a -10.6 mV of Zeta potential, CLT-15 was optimized. To determine CLT and curcumin, the simultaneous UV calibration method was created. Overall, the DSC study indicated the amorphous nature of the Nano Dispersion, which in turn means the successful entrapment of the CLT in the Nano Dispersion matrix. TEM images also confirmed the spherical nanoparticles. The optimized batch of drugs tagged with curcumin was compared with the plain drug Solid Dispersion Nanoparticles.

Conclusion: Together with the molecules of curcumin, the solid nano dispersion of CLT was produced, which will add to the benefits of the management of Diabetic Nephropathy. In the current study, we underline the importance of utilising both API and phytochemicals in the treatment of Diabetic Nephropathy, and we anticipate further basic research or clinical trials to support innovative treatments. It is possible to use these matrix-forming polymers for active ingredients with poor solubility, whether they are natural or synthetic. It has also been demonstrated that these carriers (PVP VA S 630 & Poloxamer) increase the dissolution rate (in-vitro).

Graphical Abstract

[1]
Kaushik R, Budhwar V, Kaushik D. An overview on recent patents and technologies on solid dispersion. Recent Pat Drug Deliv Formul 2019; 1-13.
[PMID: 31951172]
[2]
Lipinski C. Poor aqueous solubility: an industry wide problem in drug discovery. Am Pharm Rev 2002; 1-16.
[3]
Minocha S, Pahwa S, Arora V. SOlubility enhancement of poorly water soluble drugs by various techniques. J Biomed Pharma Res 2019; pp. 13-9.
[4]
Jermain SV, Brough C, Williams RO. Amorphous solid dispersions and nanocrystal technologies for poorly water-soluble drug delivery:An Update. Int J Pharm 2017; 1-63.
[PMID: 29128423]
[5]
Zhang S, Sun Y, Zhou L, Jiang Z, Yang X, Feng Y. Osmotic pump tablets with solid dispersions synergized by hydrophilic polymers and mesoporous silica improve in vitro/in vivo performance of cilostazol. Int J Pharm 2020; 588: 119759.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119759] [PMID: 32800938]
[6]
Sawicki E, Schellens JHM, Beijnen JH, Nuijen B. Inventory of oral anticancer agents: Pharmaceutical formulation aspects with focus on the solid dispersion technique. Cancer Treat Rev 2016; 50: 247-63.
[http://dx.doi.org/10.1016/j.ctrv.2016.09.012] [PMID: 27776286]
[7]
Sonal Mazumder AkD, Naresh pavurala. Enhanced dissolution of poorly soluble antiviral drugs from nanoparticles of cellulose acetate-based solid dispersion matrices. Asian j pharmaceutical sciences 2017; 532-41.
[8]
Nadia Saffoon RU, Huda NH, Sutradhar KB. Enhancement of oral bioavailability and solid dispersion: A review. J Appl Pharm Sci 2011; 13-20.
[9]
Rawat A, Verma S, Kaul M, Saini S. Formulation, evaluation and optimization of solid dispersion of glipizide using face centered central composite design. Int J Pharm Pharm Sci 2011; 475-82.
[10]
Andrews GP, Qian K, Jacobs E, Jones DS, Tian Y. High drug loading nanosized amorphous solid dispersion (NASD) with enhanced in vitro solubility and permeability: Benchmarking conventional ASD. Int J Pharm 2023; 632: 122551.
[http://dx.doi.org/10.1016/j.ijpharm.2022.122551] [PMID: 36581107]
[11]
Bhujbal SV, Mitrab B nemr U, et al. Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies. Acta Pharm 2021; 11(8): 2505-36.
[12]
Murdande SB, Pikal MJ, Shanker RM, Bogner RH. Solubility advantage of amorphous pharmaceuticals: I. A Thermodynamic analysis. J Pharm Sci 2010; 99(3): 1254-64.
[13]
Jog R, Burgess DJ. Pharmaceutical amorphous nanoparticles. J Pharm Sci 2016; 1-27.
[PMID: 27816266]
[14]
Araki K, Yoshizumi M, Kimura S, et al. Application of a microreactor to pharmaceutical manufacturing: Preparation of amorphous curcumin nanoparticles and controlling the crystallinity of curcumin nanoparticles by ultrasonic treatment. AAPS PharmSciTech 2020; 21(1): 17.
[http://dx.doi.org/10.1208/s12249-019-1418-8] [PMID: 31811523]
[15]
Maity SL, Chakraborti S. Formulation, physicochemical characterization and antidiabetic potential of naringenin-loaded poly D, L lactide-co-glycolide (N-PLGA) nanoparticles. Eur Polym J 2020; 1-10.
[16]
Umerska A, Gaucher C, Oyarzun-Ampuero F, Fries-Raeth I. Polymeric nanoparticles for increasing oral bioavailability of curcumin. Antioxidants 2018; 4(4): 46.
[17]
Robyn J, Tapp GD, Shaw JE, et al. Albuminuria is evident in the early stages of diabetes onset: Results from the australian diabetes, obesity, and lifestyle study. Am J Kidney Dis 2004; 792-8.
[18]
Lim AK. Diabetic nephropathy – complications and treatment. Int J Nephrol Renovasc Dis 2021; 361-81.
[19]
Hu Q, Chen Y, deng X, et al. Diabetic nephropathy: Focusing on pathological signals, clinical treatment, and dietary regulation. Biomed Pharmacother 2023; 1-16.
[20]
Frimodt-Møller PRaM. Clinical features and natural course of diabetic nephropathy. diabetic nephropathy. Denmark: Springer International Publishing AG, part of Springer Nature. 2019; pp. 21-32.
[21]
Chen S, Chen L, Jiang H. Integrated bioinformatics and clinical correlation analysis of key genes, pathways, and potential therapeutic agents related to diabetic nephropathy. Hindawi-Disease Markers 2022; 2022: 9204201.
[22]
Mohamed AF, Sayed HM, Zaki HF, Safar MM. Modulation of toll-like receptor 4/nuclear factor-kappa b, nuclear factor erythroid 2-related factor 2/hemeoxygenase-1, and phosphoinositide 3-kinase/akt signaling by cilostazol mitigates lipopolysaccharide-induced septic acute kidney injury. Bull Fac Pharm Cairo Univ 2023; 60(2): 1-13.
[23]
Lichao G, Qiang L, Yujie W, et al. Research on mechanism of curcumin with chitosan nanoparticles in regulating the activity of podocytes in diabetic nephropathy through alleviating oxidative stress and inflammation. Sci Adv Mater 2022; 14(4): 752-9.
[http://dx.doi.org/10.1166/sam.2022.4249]
[24]
Chopra H, Dey PS, Das D, et al. Curcumin nanoparticles as promising therapeutic agents for drug targets. Molecules 2021; 26(16): 4998.
[http://dx.doi.org/10.3390/molecules26164998] [PMID: 34443593]
[25]
Dagar N, Das P, Bisht P, Taraphdar AK, Velayutham R, Arumugam S. Diabetic nephropathy: A twisted thread to unravel. Life Sci 2021; 278: 119635.
[http://dx.doi.org/10.1016/j.lfs.2021.119635] [PMID: 34015285]
[26]
Tiwari RK, Pandey RK, Shukla SS. A review on mechanism and plants used for diabetic nephropathy: A curse of diabetes. Mintage J Pharmaceutical & Medical Sciences 2019; pp. 5-13.
[27]
Tsabang N, Yedjou CG, Tsambang L, et al. Treatment of diabetes and/or hypertension using medicinal plants in cameroon. Med Aromat Plants 2015; (2): 1-15.
[PMID: 26550547]
[28]
Patel RUV. Spectrophtometric methods for simultaneous estimation of telmisartan and cilostazol in synthetic mixture. AN I J PHARMA SCI 2015; pp. 276-91.
[29]
Damor D, Mittal K, Patel B, Mashru R. Method development and validation of simultaneous estimation of cilostazol and telmisartan. Research & Reviews. J Pharm Anal 2015; 4(3): 41-8.
[30]
Gaikwad A, Shelar MU, Kadam J, Andhale G, Singh S. Development and validation of simultaneous uv-spectrophotometric method for the determination of resveratrol and piperine in pharmaceutical dosage form. J Pharm Negat Results 2022; 13(8): 4141-50.
[31]
Fan S, Nedev H, Vijayan R, Iorga BI, Beckstein O. Precise force-field-based calculations of octanol-water partition coefficients for the SAMPL7 molecules. J Comput Aided Mol Des 2021; 35(7): 853-70.
[http://dx.doi.org/10.1007/s10822-021-00407-4] [PMID: 34232435]
[32]
Jin GH. Role of surfactant micellization for enhanced dissolution of poorly water-soluble cilostazol using poloxamer 407-based solid dispersion via the anti-solvent method. MDPI Pharmaceutics. 2021; pp. 1-14.
[33]
Dong W, Su X, Xu M, Hu M, Sun Y, Zhang P. Preparation, characterization, and in vitro/vivo evaluation of polymer-assisting formulation of atorvastatin calcium based on solid dispersion technique. Asian J Pharmaceutical Sciences 2018; pp. 546-54.
[34]
Yang R, Zhang GGZ, Zemlyanov DY, Purohit HS, Taylor LS. Release mechanisms of amorphous solid dispersions: Role of drug-polymer phase separation and morphology. J Pharm Sci 2023; 112(1): 304-17.
[http://dx.doi.org/10.1016/j.xphs.2022.10.021] [PMID: 36306863]
[35]
Priyadarsini M, Avula PR. Quality by design approach for development of amorphous solid dispersions of efavirenz by melt-quench technique. Nat Volatiles & Essent Oils 2022; 9(3): 43-59.
[36]
Ryu S, Park S, Lee HY, Lee H, Cho CW, Baek JS. Biodegradable nanoparticles-loaded plga microcapsule for the enhanced encapsulation efficiency and controlled release of hydrophilic drug. Int J Mol Sci 2021; 22(6): 2792.
[http://dx.doi.org/10.3390/ijms22062792] [PMID: 33801871]
[37]
Kumar A, Sandhya S, Kar NR, Sahoo S, Behera MP, Shaw RK. Nanoparticulate system of novel taxane derivatives as in-vitro evaluation and characterization. J Clinical Otorhinolaryngology 2023; 27(1): 859-71.
[38]
Nagai N, Yoshioka C, Ito Y, Funakami Y, Nishikawa H, Kawabata A. Intravenous administration of cilostazol nanoparticles ameliorates acute ischemic stroke in a cerebral ischemia/reperfusion-induced injury model. Int J Mol Sci 2015; 16(12): 29329-44.
[http://dx.doi.org/10.3390/ijms161226166] [PMID: 26690139]
[39]
Aghrbi I, Fülöp V, Jakab G, Kállai-Szabó N, Balogh E, Antal I. Nanosuspension with improved saturated solubility and dissolution rate of cilostazol and effect of solidification on stability. J Drug Deliv Sci Technol 2021; 61: 102165.
[http://dx.doi.org/10.1016/j.jddst.2020.102165]
[40]
Jakubowska E, Milanowski B, Lulek J. A systematic approach to the development of cilostazol nanosuspension by liquid antisolvent precipitation (lasp) and its combination with ultrasound. Int J Mol Sci 2021; 22(22): 12406.
[http://dx.doi.org/10.3390/ijms222212406] [PMID: 34830298]
[41]
Guner G, Amjad A, Berrios M, Kannan M, Bilgili E. Nanoseeded desupersaturation and dissolution tests for elucidating supersaturation maintenance in amorphous solid dispersions. Pharmaceutics 2023; 15(2): 450.
[http://dx.doi.org/10.3390/pharmaceutics15020450] [PMID: 36839772]
[42]
Rudraraj SV. Disintegration mediated controlled release supersaturating solid dispersion formulation of an insoluble drug: Design, development, optimization, and in vitro evaluation. AAPS PharmSciTech 2014; 1-13.
[PMID: 25190361]
[43]
Sawafta O, Alhadid S, Abu Awwad IA, Migdadi E, Aljaberi A. Impact of the manufacturing technique on the dissolution-enhancement functionality of PEG4000 in Cilostazol tablets. Pharmacia 2021; 68(1): 243-50.
[http://dx.doi.org/10.3897/pharmacia.68.e62465]
[44]
Nemr AA. EL-MAHROUK GM, EL-MAHROUK HA. Development and evaluation of surfactant-based elastic vesicular system for transdermal delivery of Cilostazole: ex-vivo permeation and histopathological evaluation studies. J Liposome Res 2021; 1-14.
[45]
Sedik AA, Amer AA. Modulatory effects of cilostazol; an nrf2/ho-1 activator against nafld in rats confirmed by molecular docking and ftir studies. Egypt J Chem 2022; 65(12): 493-508.
[46]
Karan T, Erenler R, Bozer BM. Synthesis and characterization of silver nanoparticles using curcumin: Cytotoxic, apoptotic, and necrotic effects on various cell lines. De Gruyeter 2022; 77(7-8c): 243-350.
[47]
Baas J, Senninger N, Elser H. The reticuloendothelial system. An overview of function, pathology, and recent methods of measurement. Z Gastroenterol 1994; 32(2): 117-23.
[PMID: 8165827]
[48]
Lu M, Yin N, Liu W, Cui X, Chen S, Wang E. Curcumin ameliorates diabetic nephropathy by suppressing nlrp3 inflammasome signaling. Biomed Research Inernational. 2017; p. 1-11.
[49]
Terife G, Wang P, Faridi N, Gogos CG. Hot melt mixing and foaming of soluplus® and indomethacin. Polym Eng Sci 2012; 52(8): 1629-39.
[http://dx.doi.org/10.1002/pen.23106]
[50]
Elvina M, Butar-Butar T, Wathoni N, Rathi H, Wardhan YG. Solid dispersion technology for improving the solubility of antiviral drugs. Pharmaceutical Sciences and Research 2023; 10(1): 1-19.

© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version249msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[02:06:27] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[02:06:28] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[02:06:28] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[02:06:28] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (92.78ms)time
  • Application (157ms)time
  • 1 x Application (62.79%)
    157ms
    1 x Booting (37.21%)
    92.78ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    31 statements were executed, 2 of which were duplicates, 29 unique. Show only duplicated73.65ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('314555251','',1,1740362787,1740362787) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740362787
      890μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('314555251','/article/133009',1,1740362787,1740362787)
      130μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 314555251 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314555251) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 314555251 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314555251) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 314555251 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314555251) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 314555251 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314555251) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 314555251 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314555251) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 314555251 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314555251) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 314555251 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314555251) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 314555251 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314555251) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 314555251 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314555251) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 314555251 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314555251) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 314555251 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314555251) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 314555251 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314555251) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 314555251 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314555251) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 314555251 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314555251) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 314555251 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314555251) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 314555251 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314555251) limit 1
      10.58msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 314555251
      • 1: 314555251
      • 2: 314555251
      • 3: 314555251
      • 4: 314555251
      • 5: 314555251
      • 6: 314555251
      • 7: 314555251
      • 8: 314555251
      • 9: 314555251
      • 10: 314555251
      • 11: 314555251
      • 12: 314555251
      • 13: 314555251
      • 14: 314555251
      • 15: 314555251
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=133009
      660μsalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 161 limit 1
      660μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 161
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=161) and sj.journal_id!=161 group by `j`.`nid`) as `aggregate_table`
      1.01msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=161) and sj.journal_id!=161 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      810μsalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=161) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.3msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=161) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.13msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '133009'
      210μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 133009
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '133009'
      3.44msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 133009
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '133009' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.82msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 133009
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      270μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      460μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 161 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      35.68msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 161 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      2.66msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 161 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      1.39msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 133009 limit 1
      190μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 133009
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 133009 and content_type = 'article' order by status desc limit 1
      250μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 218902 limit 1
      220μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 218902
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      240μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CNANOM' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      280μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CNANOM
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '133009' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      430μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '113' and is_uploaded = 1 and issue_id = 12733 order by cast(first_page as SIGNED) desc limit 1
      440μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 113
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '131' and is_uploaded = 1 and issue_id = 12733 order by cast(first_page as SIGNED) asc limit 1
      420μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 131
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      220μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      290μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 133009 limit 1
      2.33msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 133009
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 161 and `b`.`banner_from_date` <= 1740362787 and `b`.`banner_to_date` >= 1740362787 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      2.32msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 161
      • 3: 1740362787
      • 4: 1740362787
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 161 and `b`.`banner_from_date` <= 1740362788 and `b`.`banner_to_date` >= 1740362788 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.6msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 161
      • 3: 1740362788
      • 4: 1740362788
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='f88de4157c761fe6f6b40dd30d459869'
      320μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        WKXybjFDkS14SA25cRx5Iq1Dvpx8qB3YTItV9Kfm
        uc_cart_id
        f88de4157c761fe6f6b40dd30d459869
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/133009" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/133009
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Mon, 24 Feb 2025 02:06:27 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Im50UlcrdkNra1RXNStWbFFVVS8wNmc9PSIsInZhbHVlIjoiL1Z2Qk5RM2dEMUYzTEV6S1k4VERxVFNKTlA1OVBXbEM5ZnVET2tDS000MTNvbjVyY2MweEZuYjQvUURPSjBNM3hST0dYcmEzVnJ6ZU5mbGtkWW5DUDhpZlBGOUpxWGh0TGNSUnd6TG5TeWxWVFFHNzZQeEdMZVJYdEx4RjkvWlIiLCJtYWMiOiIzOGNjYmIwMzE5YWQ5YTJhMzYzYTdjMTVlZDkxOTAyN2ZlZThmY2UxMThhN2U3ZjdiOGRmZDM5YTE2OGEwZjBkIiwidGFnIjoiIn0%3D; expires=Wed, 26 Feb 2025 14:06:28 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6Im50UlcrdkNra1RXNStWbFFVVS8wNmc9PSIsInZhbHVlIjoiL1Z2Qk5RM2dEMUYzTEV6S1k4VERxVFNKTlA1OVBXbEM5ZnVET2tDS000MTNvbjVyY2MweEZuYjQvUURPSjBNM3hST0dYc" 1 => "alphaeurekaselectnet_session=eyJpdiI6IndJcHhjenZsN0QzTDZWRmZZY2ZNRkE9PSIsInZhbHVlIjoiYXRGc28xbFlFN2JZWUJJbnhENENKWGFVa3NUOW5uL0EwaWZBb2xKUXI5NlZHTU80OTA5d3VFYUhET0VxZFVwMkZHMGduSk84REw0Y3lBOHUxNE5CWE00dUluV3VkVmlkdXM5RzU5NlUzWjI4WC80elR4STI0RWRGaVg4bG1xTWYiLCJtYWMiOiIyYTFkMDFiOGRlMDBmMGUzZWVjOTYxOWRjMzA2MTYyOGY1ZjQ1OWMzMDYxYTg0MDMzMTNhNTlmYTIyOThiMTdiIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IndJcHhjenZsN0QzTDZWRmZZY2ZNRkE9PSIsInZhbHVlIjoiYXRGc28xbFlFN2JZWUJJbnhENENKWGFVa3NUOW5uL0EwaWZBb2xKUXI5NlZHTU80OTA5d3VFYUh" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Im50UlcrdkNra1RXNStWbFFVVS8wNmc9PSIsInZhbHVlIjoiL1Z2Qk5RM2dEMUYzTEV6S1k4VERxVFNKTlA1OVBXbEM5ZnVET2tDS000MTNvbjVyY2MweEZuYjQvUURPSjBNM3hST0dYcmEzVnJ6ZU5mbGtkWW5DUDhpZlBGOUpxWGh0TGNSUnd6TG5TeWxWVFFHNzZQeEdMZVJYdEx4RjkvWlIiLCJtYWMiOiIzOGNjYmIwMzE5YWQ5YTJhMzYzYTdjMTVlZDkxOTAyN2ZlZThmY2UxMThhN2U3ZjdiOGRmZDM5YTE2OGEwZjBkIiwidGFnIjoiIn0%3D; expires=Wed, 26-Feb-2025 14:06:28 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6Im50UlcrdkNra1RXNStWbFFVVS8wNmc9PSIsInZhbHVlIjoiL1Z2Qk5RM2dEMUYzTEV6S1k4VERxVFNKTlA1OVBXbEM5ZnVET2tDS000MTNvbjVyY2MweEZuYjQvUURPSjBNM3hST0dYc" 1 => "alphaeurekaselectnet_session=eyJpdiI6IndJcHhjenZsN0QzTDZWRmZZY2ZNRkE9PSIsInZhbHVlIjoiYXRGc28xbFlFN2JZWUJJbnhENENKWGFVa3NUOW5uL0EwaWZBb2xKUXI5NlZHTU80OTA5d3VFYUhET0VxZFVwMkZHMGduSk84REw0Y3lBOHUxNE5CWE00dUluV3VkVmlkdXM5RzU5NlUzWjI4WC80elR4STI0RWRGaVg4bG1xTWYiLCJtYWMiOiIyYTFkMDFiOGRlMDBmMGUzZWVjOTYxOWRjMzA2MTYyOGY1ZjQ1OWMzMDYxYTg0MDMzMTNhNTlmYTIyOThiMTdiIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IndJcHhjenZsN0QzTDZWRmZZY2ZNRkE9PSIsInZhbHVlIjoiYXRGc28xbFlFN2JZWUJJbnhENENKWGFVa3NUOW5uL0EwaWZBb2xKUXI5NlZHTU80OTA5d3VFYUh" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "WKXybjFDkS14SA25cRx5Iq1Dvpx8qB3YTItV9Kfm" "uc_cart_id" => "f88de4157c761fe6f6b40dd30d459869" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/133009" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-24 02:06:28GET/article/133009414311