Generic placeholder image

Pharmaceutical Nanotechnology

Editor-in-Chief

ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

Research Article

Optimized Nanoparticles for Enhanced Oral Bioavailability of a Poorly Soluble Drug: Solid Lipid Nanoparticles Versus Nanostructured Lipid Carriers

Author(s): Manal K.M. Darwish, Amal S.M. Abu El-Enin and Kamilia H.A. Mohammed*

Volume 10, Issue 1, 2022

Published on: 18 March, 2022

Page: [69 - 87] Pages: 19

DOI: 10.2174/2211738510666220210110003

Price: $65

Abstract

Introduction: Rosuvastatin calcium (ROSCa) is an anti-hyperlipidemic drug with only 20% oral bioavailability due to its low solubility and high first-pass metabolism. Therefore, the main purpose of this work was to compare solid lipid nanoparticles to nanostructured lipid carriers and evaluate their effect on solubility improvement and hence the bioavailability of a model insoluble drug.

Methods: Different nanosuspensions were formulated using high-speed homogenization and ultrasonication techniques, using Apifil as solid lipid and Maisine as liquid lipid. The effect of different variables on quality attributes (particle size, entrapment efficiency (EE), and in vitro release) was studied using the Box-Behnken design. Then, the optimized nanoparticles were lyophilized, filled into capsules, and evaluated. Finally, the optimized formula was clinically evaluated in six healthy human volunteers.

Results: It was observed that the variables had a great impact on EE and particle size. Nanoparticles showed maximum particles of 180.3 nm, and % EE ranged from 40.77% to 91.67%. Capsules loaded with NLCs were found to be more stable than those loaded with SLNs. The clinical study of NLCs-ROSCa showed an enhancement in the C max (8.92 ng/ml) compared to the commercial product (2.56 ng/ml) with approximately 349% relative bioavailability.

Conclusion: ROSCa was successfully encapsulated in SLNs and NLCs. The optimized NLCs formulation showed improved quality attributes compared to SLNs. Thus, NLCs loaded formulations could be an effective oral drug delivery system to enhance the bioavailability of insoluble drugs.

Keywords: Rosuvastatin, solid lipid nanoparticle, nanostructured lipid carriers, optimization, Box-Behnken design, entrapment efficiency, particle size, oral bioavailability, clinical evaluation.

« Previous
Graphical Abstract

[1]
Nelson RH. Hyperlipidemia as a risk factor for cardiovascular disease. Prim Care 2013; 40(1): 195-211.
[http://dx.doi.org/10.1016/j.pop.2012.11.003] [PMID: 23402469]
[2]
Balakumar K, Raghavan CV. selvan NT, prasad RH, Abdu S. Self nanoemulsifying drug delivery system (SNEDDS) of rosuvastatin calcium: Design, formulation, bioavailability and pharmacokinetic evaluation. Colloids Surf B Biointerfaces 2013; 112: 337-43.
[http://dx.doi.org/10.1016/j.colsurfb.2013.08.025] [PMID: 24012665]
[3]
Jain S, Patel N, Lin S. Solubility and dissolution enhancement strategies: Current understanding and recent trends. Drug Dev Ind Pharm 2015; 41(6): 875-87.
[http://dx.doi.org/10.3109/03639045.2014.971027] [PMID: 25342479]
[4]
Beniwal A, Choudhary H. Rosuvastatin calcium-loaded Solid Lipid Nanoparticles (SLN) using design of experiment approach for oral delivery. Inter J Chem Life Sci 2017; 6(5): 2029-38.
[http://dx.doi.org/10.21746/ijcls.2017.5.1]
[5]
Khan I, Saeed K, Khan I. .Nanoparticles: Properties, applications and toxicities. Arabian J hem 2019; 12(7): 908-31.
[6]
Ekambaram P, Sathali AA, Priyanka K. Solid lipid nanoparticles: A review. Sci Revs Chem Commun 2012; 2(1): 80-102.
[7]
Potta SG, Minemi S, Nukala RK, et al. Development of solid lipid nanoparticles for enhanced solubility of poorly soluble drugs. J Biomed Nanotechnol 2010; 6(6): 634-40.
[http://dx.doi.org/10.1166/jbn.2010.1169] [PMID: 21361127]
[8]
Kaur S, Nautyal U, Singh R, Singh S, Devi A. Nanostructure Lipid Carrier (NLC): The new generation of lipid nanoparticles. Asian Pac J Health Sci 2015; 2(2): 76-93.
[http://dx.doi.org/10.21276/apjhs.2015.2.2.14]
[9]
Shah NV, Seth AK, Balaraman R, Aundhia CJ, Maheshwari RA, Parmar GR. Nanostructured lipid carriers for oral bioavailability enhancement of raloxifene: Design and in vivo study. J Adv Res 2016; 7(3): 423-34.
[http://dx.doi.org/10.1016/j.jare.2016.03.002] [PMID: 27222747]
[10]
Kopac T, Bozgeyik K, Flahaut E. Adsorption and interactions of the bovine serum albumin-double walled carbon nanotube system. J Mol Liq 2018; 1(252): 1-8.
[http://dx.doi.org/10.1016/j.molliq.2017.12.100]
[11]
Park SJ. Protein–nanoparticle interaction: Corona formation and conformational changes in proteins on nanoparticles. Int J Nanomed 2020; 15: 5783-802.
[http://dx.doi.org/10.2147/IJN.S254808] [PMID: 32821101]
[12]
Kopac T. Protein corona, understanding the nanoparticle-protein interactions and future perspectives: A critical review. Int J Biol Macromol 2021; 169(169): 290-301.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.12.108] [PMID: 33340622]
[13]
Chaudhary HM, Jadhav KR, Kadam VJ. Formulation and evaluation of nanostructured lipid carriers containing glipizide. World J Pharm Pharm Sci 2016; 5(4): 1424-37.
[14]
Gaba B, Fazil M, Khan S, Ali A, Baboota S, Ali J. Nanostructured lipid carrier system for topical delivery of terbinafine hydrochloride. Bull Fac Pharm Cairo Univ 2015; 53(2): 147-59.
[http://dx.doi.org/10.1016/j.bfopcu.2015.10.001]
[15]
Praveen S, Gowda DV, Srivastava A, Osmani RA. Formulation and evaluation of nanostructured lipid carrier (NLC) For glimepiride. Pharm Lett 2016; 8(6): 304-9.
[16]
Bhagawati ST, Varsha NS. Formulation and in-vitro evaluation of pravastatin solid lipid nanoparticles. Int J Nanotechnol Eng Med 2017; 2(6): 113-9.
[http://dx.doi.org/10.25141/2474-8811-2017-6.0113]
[17]
Kamble SS, Gambhire MS, Gujar KN. Optimization and development of candesartan cilexetil loaded solid lipid nanoparticle for the treatment of hypertension. J Pharm Biosci 2015; 3: 53-64.
[18]
Nair R, Kumar ACK, Priya VK, Yadav CM, Raju PY. Formulation and evaluation of chitosan solid lipid nanoparticles of carbamazepine. Lipids Health Dis 2012; 11(72): 72.
[http://dx.doi.org/10.1186/1476-511X-11-72] [PMID: 22695222]
[19]
Soma D, Attari Z, Reddy MS, Damodaram A, Koteshwara KB. Solid lipid nanoparticles of irbesartan: Preparation, characterization, optimization and pharmacokinetic studies. Braz J Pharm Sci 2017; 53(1): 1-10.
[http://dx.doi.org/10.1590/s2175-97902017000115012]
[20]
Tao C, Cheng H, Zhou K, Luo Q, Guo L, Chen W, et al. Preparation and characterization of Biochanin A loaded solid lipid nanoparticles. Asian J Pharm 2012; 6(4): 275-81.
[http://dx.doi.org/10.4103/0973-8398.107563]
[21]
Choi K, Choe J, Suh S, Ko S. Positively charged nanostructured lipid carriers and their effect on the dissolution of poorly soluble drugs 2016; 21(672): 1-12.
[22]
Darwish MKM, Abu El-Enin ASM, Mohammed KHA. Formulation, optimization, and evaluation of raft-forming formulations containing Nizatidine. Drug Dev Ind Pharm 2019; 45(4): 651-63.
[http://dx.doi.org/10.1080/03639045.2019.1569033] [PMID: 30638411]
[23]
Patel RJ, Patel ZP. Formulation, optimization and evaluation of nanostructured lipid carrier containing valsartan. Inter J Pharmaceu Sci Nanotechnol 2013; 6(2): 2077-86.
[24]
Mazuryka J, Deptułaa T, Polchi A, et al. Rapamycin-loaded solid lipid nanoparticles: Morphology and impact of the drug loading on the phase transition between lipid polymorphs. Colloids Surf A Physicochem Eng Asp 2016; 502: 54-65.
[http://dx.doi.org/10.1016/j.colsurfa.2016.05.017]
[25]
Chaturvedi SP, Kumar V. Differential Scanning Calorimetry as a tool to establish formation of Lipid Nanoparticles (NLC and SLN). Res J Pharm Biol Chem Sci 2012; 3(4): 1475-81.
[26]
Padhye SG, Nagarsenker MS. Simvastatin solid lipid nanoparticles for oral delivery: Formulation development and in vivo evaluation. Indian J Pharm Sci 2013; 75(5): 591-8.
[PMID: 24403661]
[27]
Supriya A, Sundaraseelan J, Murthy BRS, Priya MB. Formulation and evaluation of capsules of Asenapine maleate loaded chitosan nanoparticles. Acta Sci Pharmaceut Sci 2018; 2(3): 29-37.
[28]
Londhe V, Save S. Zaltoprofen loaded solid lipid nanoparticles for topical delivery: Formulation design, in vitro and ex vivo evaluation. MOJ Bioequiv Availab 2017; 4(2): 00065.
[http://dx.doi.org/10.15406/mojbb.2017.04.00065]
[29]
Enriquez GG, Orawiec BA, Rizvi SAA, Do DP. Formulation development and in vitro evaluation of oral extended-release capsules containing biodegradable microspheres. J Nanomed Nanotechnol 2014; 5(3): 208.
[http://dx.doi.org/10.4172/2157-7439.1000208]
[30]
Ponnuraj R, Janakiraman K, Gopalakrishnan S, Arumugam A. Formulation and development of capsules containing rosuvastatin calcium nanoparticles and epigallocatechin gallate nanoparticles. Indo American J Pharmaceut Res 2015; 5(06): 2217-31.
[31]
Dhoranwala KA, Shah P, Shah S. Formulation optimization of rosuvastatin calcium-loaded solid lipid nanoparticles by 32 full-factorial design. Nano World J 2015; 1(4): 112-21.
[32]
Naglakshmi S, Shanmuganathan S, Sandhya K, Anbarasan B. Design, development and characterization of nano structured lipid carrier for topical delivery of aceclofenac. Indian J Pharmaceut Educ Res 2018; 52(4): 581-6.
[33]
Smitha G, Reddy SC, Kumar DS, Kumar JS, Jukanti R, et al. Rosuvastatin calcium quantification in rat serum with the aid of RP-HPLC: Method development and validation. IOSR J Pharm Biol Sci 2015; 10(5): 23-8.
[34]
Alam S, Aslam M, Khan A, et al. Nanostructured lipid carriers of pioglitazone for transdermal application: From experimental design to bioactivity detail. Drug Deliv 2016; 23(2): 601-9.
[http://dx.doi.org/10.3109/10717544.2014.923958] [PMID: 24937378]
[35]
Cirri M, Maestrini L, Maestrelli F, et al. Design, characterization and in vivo evaluation of nanostructured lipid carriers (NLC) as a new drug delivery system for hydrochlorothiazide oral administration in pediatric therapy. Drug Deliv 2018; 25(1): 1910-21.
[http://dx.doi.org/10.1080/10717544.2018.1529209] [PMID: 30451015]
[36]
United States Pharmacopeia; National Formulary USP 35-NF 30. Rockville, MD: The United States Pharmacopeial Convention 2012.
[37]
Abousamra MM, Mohsen AM. Solid lipid nanoparticles and nanostructured lipid carriers of tolnaftate: Design, optimization and in-vitro evaluation. Int J Pharm Pharm Sci 2015; 8(1): 380-5.
[38]
Zhang C, Gu C, Peng F, et al. Preparation and optimization of triptolide-loaded solid lipid nanoparticles for oral delivery with reduced gastric irritation. Molecules 2013; 18(11): 13340-56.
[http://dx.doi.org/10.3390/molecules181113340] [PMID: 24172242]
[39]
Anarjan N, Jafarizadeh-Malmiri H, Nehdi IA, Sbihi HM, Al-Resayes SI, Tan CP. Effects of homogenization process parameters on physicochemical properties of astaxanthin nanodispersions prepared using a solvent-diffusion technique. Int J Nanomed 2015; 10: 1109-18.
[PMID: 25709435]
[40]
Jelvehgari M, Nokhodchi A, Rezapour M, Valizadeh H. Effect of formulation and processing variables on the characteristics of tolmetin microspheres prepared by double emulsion solvent diffusion method. Indian J Pharm Sci 2010; 72(1): 72-8.
[http://dx.doi.org/10.4103/0250-474X.62251] [PMID: 20582193]
[41]
Gönüllü Ü, Üner M, Yener G, Karaman EF, Aydoğmuş Z. Formulation and characterization of solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsion of lornoxicam for transdermal delivery. Acta Pharm 2015; 65(1): 1-13.
[http://dx.doi.org/10.1515/acph-2015-0009] [PMID: 25781700]
[42]
Syed A, Devi VK. Transdermal delivery of azathioprine by solid lipid nanoparticles: In-vitro and ex-vivo studies. Int J Pharm Sci Res 2019; 10(2): 586-98.
[43]
Emami J, Mohiti H, Hamishehkar H, Varshosaz J. Formulation and optimization of solid lipid nanoparticle formulation for pulmonary delivery of budesonide using Taguchi and Box-Behnken design. Res Pharm Sci 2015; 10(1): 17-33.
[PMID: 26430454]
[44]
Sharma N, Madan P, Lin S. Effect of process and formulation variables on the preparation of parenteral paclitaxel-loaded biodegradable polymeric nanoparticles: A co-surfactant study. Asian J Pharmaceut Sci 2016; 11(3): 404-16.
[45]
Garse H, Jagtap P, Dand N, Kadam V. Studies on lipid nanoparticle formulation of antihyperlipidemic drug. World J Pharm Sci 2015; 3(3): 438-47.
[46]
D’Souza S. A review of in vitro drug release test methods for nano-sized dosage forms. Advances Pharmaceut 2014 2014.
[http://dx.doi.org/10.1155/2014/304757]
[47]
Müller RH, Mäder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery - a review of the state of the art. Eur J Pharm Biopharm 2000; 50(1): 161-77.
[http://dx.doi.org/10.1016/S0939-6411(00)00087-4] [PMID: 10840199]
[48]
Archana D, Divya J. Preparation and characterization of atenolol laden nanoparticles. J Nanomed Res 2016; 4(2): 00084.
[49]
De M, Barbosa R, Ribeiro LNM, Casadei BR, et al. Solid lipid nanoparticles for dibucaine sustained release. Pharmaceutics 2018; 10(4): 231.
[http://dx.doi.org/10.3390/pharmaceutics10040231]
[50]
Seyfoddin A, Al-Kassas R. Development of solid lipid nanoparticles and nanostructured lipid carriers for improving ocular delivery of acyclovir. Drug Dev Ind Pharm 2013; 39(4): 508-19.
[http://dx.doi.org/10.3109/03639045.2012.665460] [PMID: 22424312]
[51]
Luo W, Li T, Wang C, Huang F. Discovery of Beeswax as binding agent on a 6th-century BC Chinese Turquoise-inlaid Bronze sword. J Archaeol Sci 2012; 39(5): 1227-37.
[http://dx.doi.org/10.1016/j.jas.2011.12.035]
[52]
El Maghraby GM, Elsergany RN. Fast disintegrating tablets of nisoldipine for intra-oral administration. Pharm Dev Technol 2014; 19(6): 641-50.
[http://dx.doi.org/10.3109/10837450.2013.813543] [PMID: 23841582]
[53]
Agarwal R, Malthar HP, Madhumathi CH, Reddy BC. Development and pharmacodynamic evaluation of rosuvastatin-loaded nanostructured lipid carriers for oral administration. World J Pharm Pharmaceut Sci 2015; 4(07): 699-716.
[54]
Nayak AP, Tiyaboonchai W, Patankar S, Madhusudhan B, Souto EB. Curcuminoids-loaded lipid nanoparticles: Novel approach towards malaria treatment. Colloids Surf B Biointerfaces 2010; 81(1): 263-73.
[http://dx.doi.org/10.1016/j.colsurfb.2010.07.020] [PMID: 20688493]
[55]
Kunal AG, Mallinath H, Deepak B, Pallavi SN. Lyophilization/freeze drying-A review. World J Pharm Res 2015; 4(8): 516-43.
[56]
Akhoond Zardini A, Mohebbi M, Farhoosh R, Bolurian S. Production and characterization of nanostructured lipid carriers and solid lipid nanoparticles containing lycopene for food fortification. J Food Sci Technol 2018; 55(1): 287-98.
[http://dx.doi.org/10.1007/s13197-017-2937-5] [PMID: 29358821]
[57]
El-Say KM, Hosny KM. Optimization of carvedilol solid lipid nanoparticles: An approach to control the release and enhance the oral bioavailability on rabbits. PLoS One 2018; 13(8)e0203405
[http://dx.doi.org/10.1371/journal.pone.0203405] [PMID: 30161251]
[58]
Luvai A, Mbagaya W, Hall AS, Barth JH. Rosuvastatin: A review of the pharmacology and clinical effectiveness in cardiovascular disease. Clin Med Insights Cardiol 2012; 6: 17-33.
[http://dx.doi.org/10.4137/CMC.S4324] [PMID: 22442638]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version1.83sRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[21:06:39] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[21:06:41] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[21:06:41] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[21:06:41] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (129ms)time
  • Application (1.7s)time
  • 1 x Application (92.95%)
    1.70s
    1 x Booting (7.05%)
    129ms
    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
    36 statements were executed, 4 of which were duplicates, 32 unique. Show only duplicated76.9ms
    • 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 ('59071403','',1,1740344801,1740344801) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740344801
      920μsalphaeurekaselec_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 ('59071403','/article/120788',1,1740344801,1740344801)
      580μsalphaeurekaselec_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 >= 59071403 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59071403) 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 >= 59071403 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59071403) 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 >= 59071403 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59071403) 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 >= 59071403 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59071403) 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 >= 59071403 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59071403) 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 >= 59071403 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59071403) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 59071403 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59071403) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 59071403 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59071403) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 59071403 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59071403) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 59071403 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59071403) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 59071403 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59071403) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 59071403 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59071403) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 59071403 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59071403) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 59071403 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59071403) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 59071403 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59071403) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 59071403 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59071403) limit 1
      15.57msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 59071403
      • 1: 59071403
      • 2: 59071403
      • 3: 59071403
      • 4: 59071403
      • 5: 59071403
      • 6: 59071403
      • 7: 59071403
      • 8: 59071403
      • 9: 59071403
      • 10: 59071403
      • 11: 59071403
      • 12: 59071403
      • 13: 59071403
      • 14: 59071403
      • 15: 59071403
      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=120788
      860μsalphaeurekaselec_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` = 133 limit 1
      800μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 133
      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=133) and sj.journal_id!=133 group by `j`.`nid`) as `aggregate_table`
      990μsalphaeurekaselec_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=133) and sj.journal_id!=133 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      770μsalphaeurekaselec_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=133) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.33msalphaeurekaselec_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=133) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.18msalphaeurekaselec_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` = '120788'
      870μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 120788
      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` = '120788'
      2.77msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 120788
      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` = '120788' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      1.85msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 120788
      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
      310μsalphaeurekaselec_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
      590μsalphaeurekaselec_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 = 133 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      25.27msalphaeurekaselec_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 = 133 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      5.81msalphaeurekaselec_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 = 133 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      2.38msalphaeurekaselec_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` = 120788 limit 1
      200μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 120788
      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 = 120788 and content_type = 'article' order by status desc limit 1
      220μsalphaeurekaselec_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` = 201000 limit 1
      170μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 201000
      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
      230μsalphaeurekaselec_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` = 'PNT' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      240μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: PNT
      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 = '120788' 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) )
      290μsalphaeurekaselec_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 count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '11426' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      250μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 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 count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '3177' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      230μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 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 j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59071403 and j.to_ip >=59071403 )) and ((j.from_date <= 1740344801 and j.to_date >= 1740344801 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3177) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59071403 and j.to_ip >=59071403 )) and ((j.from_date <= 1740344801 and j.to_date >= 1740344801 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3177) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59071403 and j.to_ip >=59071403 )) and ((j.from_date <= 1740344801 and j.to_date >= 1740344801 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3177)
      3.84msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 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.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59071403 and j.to_ip >=59071403 )) and ((j.from_date <= 1740344801 and j.to_date >= 1740344801 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11426) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59071403 and j.to_ip >=59071403 )) and ((j.from_date <= 1740344801 and j.to_date >= 1740344801 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11426) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59071403 and j.to_ip >=59071403 )) and ((j.from_date <= 1740344801 and j.to_date >= 1740344801 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11426)
      570μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 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.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59071403 and j.to_ip >=59071403 )) and ((j.from_date <= 1740344801 and j.to_date >= 1740344801 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 120788) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59071403 and j.to_ip >=59071403 )) and ((j.from_date <= 1740344801 and j.to_date >= 1740344801 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 120788) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59071403 and j.to_ip >=59071403 )) and ((j.from_date <= 1740344801 and j.to_date >= 1740344801 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 120788)
      550μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 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 `article` where `first_page` < '69' and is_uploaded = 1 and issue_id = 11426 order by cast(first_page as SIGNED) desc limit 1
      460μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 69
      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` > '87' and is_uploaded = 1 and issue_id = 11426 order by cast(first_page as SIGNED) asc limit 1
      390μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 87
      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'
      200μsalphaeurekaselec_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
      240μsalphaeurekaselec_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` = 120788 limit 1
      2.41msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 120788
      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` = 133 and `b`.`banner_from_date` <= 1740344801 and `b`.`banner_to_date` >= 1740344801 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.56msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 133
      • 3: 1740344801
      • 4: 1740344801
      • 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` = 133 and `b`.`banner_from_date` <= 1740344801 and `b`.`banner_to_date` >= 1740344801 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.66msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 133
      • 3: 1740344801
      • 4: 1740344801
      • 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='c72767d9431504f7ab32d7ca71ffc6c7'
      340μsalphaeurekaselec_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
        YaTovdcjNsm1sKuTmQXjKFL1LlDZ5s42AbRhU6Un
        uc_cart_id
        c72767d9431504f7ab32d7ca71ffc6c7
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/120788" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/120788
        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:9 [ "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6Ik9tTjVCTWZsTHRMbzh1TldxdDJNUmc9PSIsInZhbHVlIjoiN2dSUDNBZHZCTDllUE96VUVVY1Z1QXhoNVEwWU9jVGp0TVE3QXl5NmJuUT0iLCJtYWMiOiIxYzM3OTI4NDZhMzM3NjNkZjEwZTVkZGM3YmM4ZTNlNThiMGJjMjQ3NTg0NjUwNzJkZmJhYjFlMDlkNDFhZDliIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6Ik9tTjVCTWZsTHRMbzh1TldxdDJNUmc9PSIsInZhbHVlIjoiN2dSUDNBZHZCTDllUE96VUVVY1Z1QXhoNVEwWU9jVGp0TVE3QXl5NmJuUT0iLCJtYWMiOiIxYzM3OTI4NDZhMzM3" ] "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
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        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 => "Sun, 23 Feb 2025 21:06:41 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InlUelRUYmJaaVlpMkV2dWJqKzNCZFE9PSIsInZhbHVlIjoicWVFVXBpWGpIdDNQQW5wVDA3NzJ0Z1pIUHpBSk5oNjFNYVBhQUZpUlJ1ak9QL1QwZzVVbTc2OW5GRWlldlVsMlc5bjNYOTNTVzNkNXNuR1M2d3M2N3J2azBPYW50OGMwTzVmall0dGlmN1ZSeU8zNWhILzIxM05xREVyS2RVSGMiLCJtYWMiOiJiYjkwYmQwODRiNGU0NGQxMDE2NGNhNWUyNWQ2OThlYzFlMTdhODFmMDI0Yzg2ZmZiNWU1YzM1NzM2YmQxZmI3IiwidGFnIjoiIn0%3D; expires=Wed, 26 Feb 2025 09:06:41 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6InlUelRUYmJaaVlpMkV2dWJqKzNCZFE9PSIsInZhbHVlIjoicWVFVXBpWGpIdDNQQW5wVDA3NzJ0Z1pIUHpBSk5oNjFNYVBhQUZpUlJ1ak9QL1QwZzVVbTc2OW5GRWlldlVsMlc5bjNYO" 1 => "alphaeurekaselectnet_session=eyJpdiI6InNWS2VBSTl2dWxyNm9tOG9iMlhBb0E9PSIsInZhbHVlIjoiYXoxNDhyT0dtTFpnc0tEY3d4YmV2RHg2Tm44ZXVDTGVoM2xvNC81eHZnSTdzSXBxcUVPTXhkWnkwY3VPbW9RRm5ZcFFTYXpHcE5ocXMxdGc4OCt0dU1ZVEdncGFTUUVwNVdtaVdheGx1dUJqVGpDZHJ1b0VyZE5OTVZSajJmZEoiLCJtYWMiOiI0M2NjY2Q0NjlhZjk1MTQwYzA5Y2Y1OTg0NDVlNGIzMTMyMWE5YjMzZDk5NjgxZDViNzQ5NThkZmU0M2VkM2UyIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6InNWS2VBSTl2dWxyNm9tOG9iMlhBb0E9PSIsInZhbHVlIjoiYXoxNDhyT0dtTFpnc0tEY3d4YmV2RHg2Tm44ZXVDTGVoM2xvNC81eHZnSTdzSXBxcUVPTXhkWnk" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6InlUelRUYmJaaVlpMkV2dWJqKzNCZFE9PSIsInZhbHVlIjoicWVFVXBpWGpIdDNQQW5wVDA3NzJ0Z1pIUHpBSk5oNjFNYVBhQUZpUlJ1ak9QL1QwZzVVbTc2OW5GRWlldlVsMlc5bjNYOTNTVzNkNXNuR1M2d3M2N3J2azBPYW50OGMwTzVmall0dGlmN1ZSeU8zNWhILzIxM05xREVyS2RVSGMiLCJtYWMiOiJiYjkwYmQwODRiNGU0NGQxMDE2NGNhNWUyNWQ2OThlYzFlMTdhODFmMDI0Yzg2ZmZiNWU1YzM1NzM2YmQxZmI3IiwidGFnIjoiIn0%3D; expires=Wed, 26-Feb-2025 09:06:41 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6InlUelRUYmJaaVlpMkV2dWJqKzNCZFE9PSIsInZhbHVlIjoicWVFVXBpWGpIdDNQQW5wVDA3NzJ0Z1pIUHpBSk5oNjFNYVBhQUZpUlJ1ak9QL1QwZzVVbTc2OW5GRWlldlVsMlc5bjNYO" 1 => "alphaeurekaselectnet_session=eyJpdiI6InNWS2VBSTl2dWxyNm9tOG9iMlhBb0E9PSIsInZhbHVlIjoiYXoxNDhyT0dtTFpnc0tEY3d4YmV2RHg2Tm44ZXVDTGVoM2xvNC81eHZnSTdzSXBxcUVPTXhkWnkwY3VPbW9RRm5ZcFFTYXpHcE5ocXMxdGc4OCt0dU1ZVEdncGFTUUVwNVdtaVdheGx1dUJqVGpDZHJ1b0VyZE5OTVZSajJmZEoiLCJtYWMiOiI0M2NjY2Q0NjlhZjk1MTQwYzA5Y2Y1OTg0NDVlNGIzMTMyMWE5YjMzZDk5NjgxZDViNzQ5NThkZmU0M2VkM2UyIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6InNWS2VBSTl2dWxyNm9tOG9iMlhBb0E9PSIsInZhbHVlIjoiYXoxNDhyT0dtTFpnc0tEY3d4YmV2RHg2Tm44ZXVDTGVoM2xvNC81eHZnSTdzSXBxcUVPTXhkWnk" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "YaTovdcjNsm1sKuTmQXjKFL1LlDZ5s42AbRhU6Un" "uc_cart_id" => "c72767d9431504f7ab32d7ca71ffc6c7" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/120788" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-23 21:06:41GET/article/120788414361