{"title":"Design and development of leflunomide loaded topical microsponge gel: insights from <i>ex vivo</i> and <i>in vivo</i> inflammatory studies.","authors":"Nirmal Shah, Priyank Patel, Dipti Gohil, Rajesh Maheshwari, Chitrali Talele, Dipali Talele, Dhaivat Parikh, Jay Patwa","doi":"10.1080/10837450.2025.2525256","DOIUrl":"10.1080/10837450.2025.2525256","url":null,"abstract":"<p><p>Leflunomide, a frequently used medicament, falls under the category of disease modifying anti-rheumatoid drugs. The tablets are the only product available in the market which may lead to liver toxicity upon long-term use. Being a class II drug, there is a need of some novel formulation for minimizing systemic toxicity of drug without compromising its therapeutic potential. Microsponges possess unique characteristics that makes it a versatile drug delivery carrier. Leflunomide loaded Microsponges were prepared with matrix forming polymer (ethyl cellulose) and stabilizer (poly vinyl alcohol) using quasi-emulsion solvent diffusion method. Two independent parameters, namely concentrations of polymer and stabilizing agent, were examined using a full 3<sup>2</sup> factorial design to determine their impact on particle size and % entrapment efficiency. The optimized formulation showed promising result for particle size (48.96 µm) and entrapment efficiency (89.45%) with spherical and tiny pores on surface. The optimized gel exhibited sustained release up to 8 h (91.46 ± 3.84%) with satisfactory results of flux and permeability coefficient. The developed formulation has good anti-inflammatory properties in wistar rats and a histopathology investigation on rats' skin verified its skin compatibility. The stability study showed stable formulation up to the period of 3 months. These findings demonstrated the potential of microsponges to improve the therapeutic potential of poorly soluble leflunomide.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-12"},"PeriodicalIF":2.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Engineered gastroretentive amorphous ferulate matrix: a novel raft-forming paradigm for enhanced bioavailability.","authors":"Ruedeekorn Wiwattanapatapee, Nattawat Chavasiri, Kijja Laohawiriyakamon, Saravoot Pumjan, Nattawut Leelakanok, Arpa Petchsomrit","doi":"10.1080/10837450.2025.2525265","DOIUrl":"10.1080/10837450.2025.2525265","url":null,"abstract":"<p><p>This study aimed to enhance the solubility of ferulic acid using solid dispersion techniques and develop chewable tablets that neutralize stomach acid, form a protective gel layer, prevent gastric fluid reflux, and ensure prolonged retention in the stomach with controlled release of the active ingredient. Researchers developed solid dispersions of ferulic acid using Eudragit<sup>®</sup> E PO as a carrier, with a 1:2 w/w ratio, achieving the highest solubility (39.9 mg/mL). Chewable tablets were formulated by direct compression, incorporating sodium alginate as a gelling agent, calcium carbonate for calcium ions and carbon dioxide, HPMC as a release retardant, and mannitol as a diluent. All formulations rapidly formed a gel layer within 10 s, had a lower density than gastric fluid, and floated on 0.1 N hydrochloric acid for over 8 h. The optimal formulation demonstrated excellent physical properties, including a gel strength of 11.84 g, an acid neutralization capacity of 15.97 mEq, and reaching 80.58% over 8 h with gradual release. It exhibited significant antioxidant activity (IC<sub>50</sub> 6.74 µg/mL) in the DPPH assay and showed stronger anti-inflammatory effects in macrophage cells than indomethacin. These findings suggest this formulation could enhance ferulic acid's effectiveness in treating gastric ulcers and preventing acid reflux.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-16"},"PeriodicalIF":2.6,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Janhavi Deshmukh, Kavish Sanil, Achref Cherif, Eman A Ashour
{"title":"Development of fenofibrate solid dispersion via hot melt extrusion and 3D printing technologies.","authors":"Janhavi Deshmukh, Kavish Sanil, Achref Cherif, Eman A Ashour","doi":"10.1080/10837450.2025.2522802","DOIUrl":"10.1080/10837450.2025.2522802","url":null,"abstract":"<p><p>This study aimed to develop an amorphous solid dispersion (ASD) of fenofibrate using Hot Melt Extrusion (HME) and 3D printing to evaluate the impact of preparation methods on ASD properties. Fenofibrate (10% w/w) was processed with Soluplus<sup>®</sup> and Polyethylene oxide-N80 to produce HME filaments. These filaments were either used as feedstock for Fused Deposition Modeling (FDM) 3D printing to fabricate tablets with 90%, 70%, and 50% infill densities or milled and filled into gelatin capsules. Printability was assessed <i>via</i> a three-point bend test. The fenofibrate formulations were evaluated for drug content, physical state, surface morphology, and release profile. The SEM images of pure fenofibrate showed large cylindrical crystals while the 3D-printed tablets showed a smooth surface with no record of any crystals. This observation is in line with the DSC results and confirms the conversion of fenofibrate from crystalline to an amorphous state. The <i>in- vitro</i> drug release for the 3D printed tablets and capsules was increased 2-fold as compared to pure fenofibrate. Statistical comparisons further supported these findings, highlighting infill density as a tunable parameter for modulating release kinetics.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-11"},"PeriodicalIF":2.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruyue Dong, Xiaolu Han, Zhiqiang Tang, Xiaoxuan Hong, Hui Zhang, Nan Liu, Kun Wan, Mingyuan Li, Zengming Wang, Aiping Zheng
{"title":"Study on controlling 3D printed drug release rates based on model structural adjustment.","authors":"Ruyue Dong, Xiaolu Han, Zhiqiang Tang, Xiaoxuan Hong, Hui Zhang, Nan Liu, Kun Wan, Mingyuan Li, Zengming Wang, Aiping Zheng","doi":"10.1080/10837450.2025.2522795","DOIUrl":"10.1080/10837450.2025.2522795","url":null,"abstract":"<p><p>As an emerging technology, 3D printing facilitates the fabrication of complex preparations and enables controlled drug release. This study integrated semi-solid extrusion (SSE) and fused deposition modeling (FDM) to develop core-shell structured sustained-release tablets (CSRT) with varying release profiles, exploring how structural design influences release behavior. Propranolol hydrochloride was selected as the model drug. Drug-loaded cores with different filling rates were prepared using SSE and characterized for appearance, hardness, XRD, and release properties. Shells with varying release windows were fabricated using FDM. Subsequently, shells and cores were assembled. Micro-CT was employed for microstructural characterization, while drug assay and release properties were assessed. The results indicated that cores exhibited a good appearance, and the SSE process had no effect on the crystal type. Adjusting the filling rate allowed for slight modulation of drug release while the shell structure effectively prolonged drug release. The CSRT displayed no significant internal defects, and the assay met the United States Pharmacopoeia-National Formulary 2024 (USP-NF 2024) requirements. Adjusting release windows resulted in a sustained release ranging from 8 to 24 h, with the release profile conforming to first-order kinetics (R<sup>2</sup> values ranging from 0.961 to 0.999). These findings provide practical strategies for controlling drug release rates.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-12"},"PeriodicalIF":2.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Midhat Rehman, Saba Sohail, Zakir Ali, Ali H Alamri, Ahmed A Lahiq, Taha Alqahtani, Saleh Alyahya, Fakhar Ud Din
{"title":"Development and optimization of cilostazol loaded transethosomal gel for improved performance.","authors":"Midhat Rehman, Saba Sohail, Zakir Ali, Ali H Alamri, Ahmed A Lahiq, Taha Alqahtani, Saleh Alyahya, Fakhar Ud Din","doi":"10.1080/10837450.2025.2521055","DOIUrl":"10.1080/10837450.2025.2521055","url":null,"abstract":"<p><p>Deep vein thrombosis (DVT) is the third major leading cause of mortality and morbidity after cardiovascular disease and stroke. Cilostazol (CLZ) being one of the antiplatelet agents is effectively used in DVT. However, its oral administration is associated with several problems, such as gastrointestinal side effects and extensive first-pass metabolism. Herein, CLZ-loaded transethosomes (CLZ-TEs) were prepared and incorporated in chitosan gel (CLZ-TEG) for transdermal administration. Box-Behnken Design Expert<sup>®</sup> software was used to statistically optimize CLZ-TEs. Particle properties, Transmission electron microscopy (TEM), and Fourier Transform Infrared spectroscopy (FTIR) analyses of CLZ-TEs were accomplished followed by <i>in vitro</i> release and permeation studies and its comparison with CLZ-TEG, CLZ-dispersion (Ds) and CLZ-G. Moreover, skin irritation and pharmacokinetics studies of the optimized CLZ-TEG were executed. The optimized CLZ-TEs showed a mean particle size of 174 nm, polydispersity index of 0.173, zeta potential of -30 mV, and entrapment efficiency of 99%. TEM exhibited spherical nanovesicles and FTIR demonstrated compatibility of the excipients. Moreover, CLZ-TEG was homogeneous, smooth, and spreadable. Similarly, CLZ-TEG displayed sustained release and enhanced permeation of the CLZ. Furthermore, pharmacokinetic study showed significantly improved (<i>p</i> < 0.05) bioavailability of CLZ-TEG when compared with CLZ-G and CLZ-Ds. It was concluded that CLZ-TEG may be a potential candidate for the management of DVT.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-19"},"PeriodicalIF":2.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Investigating the <i>in vivo</i> distribution characteristics of gel-in-water nanogel emulsions and demonstrating their efficacy in treating C26 tumor-bearing mice.","authors":"Yi Zhang, Jannatul Fardous, Ryota Doi, Yuuta Inoue, Yasuhiro Ikegami, Hiroyuki Ijima","doi":"10.1080/10837450.2025.2518564","DOIUrl":"10.1080/10837450.2025.2518564","url":null,"abstract":"<p><p>Nanotechnology has been advancing drug delivery systems (DDSs) for decades. Nanoparticle DDSs, in which nanometric carriers deliver drugs to the target site, are highly valued for cancer treatment. In this study, based on nanoemulsion technology, gel-in-water (G/W) nanoemulsion was developed by using an organogel, i.e. 12-hydroxystearic acid and castor oil, followed by encapsulation of the model anticancer drug paclitaxel (PTX) within the nanogel droplets. The G/W was prepared using ultrasound and stabilized with a nonionic surfactant. The enhanced permeability and retention of G/W were investigated by encapsulating coumarin-6 and comparing it with an oil-in-water (O/W) nanoemulsion. Temporal changes in tissue distribution of both nanoemulsions were used to assess the effect of gelation on drug distribution. Regardless of the tissue type, the extraction efficiency of G/W was lower compared to O/W. The fluorescence intensity of coumarin-6 in G/W was higher compared to O/W. The size of G/W nanoparticles affects lung distribution and blood retention. PTX-loaded G/W (PTX-G/W) nanoparticles effectively treated colon cancer <i>in vivo</i>. They also exhibited antitumor activity against colon26 (C26) cells <i>in vitro</i>. The impact of particle size on the <i>in vivo</i> tissue distribution of G/W nanoemulsions suggests an improvement in drug delivery to the tumor site <i>via</i> nanoparticles.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-14"},"PeriodicalIF":2.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancing darunavir delivery: nanoformulation strategies and innovations in HIV therapy.","authors":"Shreyash R Patil, Anjana Adhyapak, Rahul Koli","doi":"10.1080/10837450.2025.2520624","DOIUrl":"10.1080/10837450.2025.2520624","url":null,"abstract":"<p><p>Darunavir, a nonpeptidic protease inhibitor, remains a cornerstone of antiretroviral therapy due to its potent activity against wild-type human immunodeficiency virus (HIV). However, its poor aqueous solubility and limited oral bioavailability, characteristic of Biopharmaceutical Classification System Class II drugs, restrict therapeutic efficacy, with an absorption rate of only 37%. To address these pharmacokinetic limitations, nanotechnology-based strategies have been explored to enhance drug solubility, systemic exposure, and targeted tissue distribution. This review critically examines the potential of nanocarrier-based formulations, including solid lipid nanoparticles, supersaturated self-nanoemulsifying drug delivery systems, lipid nanoemulsions, poly(lactic-co-glycolic acid) nanoparticles, and cubosomes, in optimizing darunavir pharmacokinetics. These approaches have demonstrated improved bioavailability, sustained drug release, lymphatic targeting, and enhanced blood-brain barrier penetration, offering promising avenues for optimizing HIV therapy while minimizing systemic toxicity. Further, this review discusses challenges associated with nanoformulation-based antiretroviral strategies, scalability, manufacturing challenges, potential toxicity, immunogenicity, long-term stability issues, and explores emerging innovations, such as multifunctional nanoparticles, targeted delivery platforms, and sustainable nanotechnology-based formulations. By systematically evaluating current advances, this analysis provides critical insights into overcoming bioavailability constraints and facilitating the clinical translation of nanocarrier-based antiretroviral therapies.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-49"},"PeriodicalIF":2.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Firas El-Saleh, Hendrik Hübscher, Sergei Trofimov, Christian Muehlenfeld
{"title":"Impact of functional-related characteristics (FRCs) of crospovidone on tablet disintegration performance.","authors":"Firas El-Saleh, Hendrik Hübscher, Sergei Trofimov, Christian Muehlenfeld","doi":"10.1080/10837450.2025.2518568","DOIUrl":"10.1080/10837450.2025.2518568","url":null,"abstract":"<p><p>Crospovidone, a widely used superdisintegrant, exists in two pharmacopeial grades - Type A (coarser particle size) and type B (finer particle size). The differences in particle size among different crospovidone grades lead to variations in functional related characteristics (FRCs), such as hydration capacity and powder flowability. The present study investigates the relative impact of crospovidone FRCs on tablet disintegration time. Multiple lots of different crospovidone grades were evaluated for their particle size distribution, hydration capacity and powder flowability. Subsequently, tablets were prepared from the different lots of crospovidone and evaluated for their disintegration time. Correlation analyses were performed to evaluate the independent effects of FRCs on disintegration time. While initial correlations showed strong interdependence among particle size, hydration capacity, and powder flowability, the decoupling of particle size as the most impacting factor revealed that hydration capacity and powder flowability had no or only limited impact on the tablet disintegration time.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-13"},"PeriodicalIF":2.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"HPMCAS-solidified supersaturated baicalin self-nanoemulsifying drug delivery systems: development and anti-colitis evaluation.","authors":"Jie Wang, Xuemei Gu, Zhiyang Lv, Jing Chen, Zihan Gao, Xinyun Hu, Wei Xiao","doi":"10.1080/10837450.2025.2518567","DOIUrl":"10.1080/10837450.2025.2518567","url":null,"abstract":"<p><p>This study developed a hydroxypropyl methylcellulose acetate succinate (HPMCAS)-functionalized supersaturated self-nanoemulsifying drug delivery system (HPMCAS-SNEDDS@BA) to address the poor solubility and bioavailability of baicalin (BA), a flavonoid with anti-colitis efficacy. The formulation was systematically optimized through solubility screening, emulsification efficiency evaluation, and pseudo-ternary phase diagram analysis. Central composite design-response surface methodology (CCD-RSM) was employed to identify the optimal SNEDDS@BA composition, followed by HPMCAS ratio optimization based on supersaturation maintenance in biorelevant media. Comprehensive characterization included emulsification performance, droplet morphology, solid-state properties, <i>in vitro</i> release, and stability. The optimized formulation (mass ratio: HPMCAS-castor oil-RH40-PEG400-BA = 151.5:20:40:40:1) generated homogeneous, transparent nanoemulsions with spherical droplets, achieving an emulsification time of 48.30 ± 0.74 s, a mean particle size of 47.77 ± 2.32 nm, and a polydispersity index (PDI) of 0.259 ± 0.007. HPMCAS-SNEDDS@BA effectively prevented premature gastric emulsification while enhancing intestinal dissolution rates and sustaining BA supersaturation. Pharmacokinetic studies demonstrated a 5.84-fold improvement in BA bioavailability compared to unmodified formulations. In a dextran sulfate sodium (DSS)-induced colitis model, HPMCAS-SNEDDS@BA outperformed BA suspension and SNEDDS@BA, normalizing colon length, reducing inflammatory cytokines, and restoring mucosal architecture. These findings validate the dual functionality of HPMCAS as a pH-responsive polymer and crystallization inhibitor, enabling targeted intestinal delivery and optimized therapeutic outcomes for ulcerative colitis.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1-16"},"PeriodicalIF":2.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hetong Wang, Wei Wang, Qin Tang, Xun Liu, Limin Zhu, Di Sun, Tingting Lin
{"title":"Enzyme-sensitive peptide KC26 modifies milk exosomes encapsulating carboplatin for the treatment of retinoblastoma.","authors":"Hetong Wang, Wei Wang, Qin Tang, Xun Liu, Limin Zhu, Di Sun, Tingting Lin","doi":"10.1080/10837450.2025.2505005","DOIUrl":"10.1080/10837450.2025.2505005","url":null,"abstract":"<p><p>Milk exosomes have also been widely used as emerging delivery vehicles for various therapeutic cargoes. Retinoblastoma (RB) is the most common primary intraocular malignancy of childhood. However, the therapeutic efficacy is severely hampered by the presence of blood-retinal barrier (BRB) and systemic side effects. Legumain (LGMN) can be used as a target for tumor microenvironment responsive delivery design and therapeutic applications. Here, a LGMN-sensitive peptide KC26-modified milk exosomes loaded with carboplatin (CBP-KC26-MExos). The system enables milk exosomes loaded with carboplatin (CBP) to reach the target cells by binding to LGMN, improves tumor targeting, enhances cellular uptake and apoptosis, inhibits cell proliferation, invasion and migration. Intravenous injection of CBP-KC26-MExos cross the BRB significantly inhibited intraocular tumor progression and reduced CBP toxicity. We have developed a 'drug-target-carrier' approach and proposed an enzyme sensitive peptide (KC26) modified milk exosomes loaded with CBP, providing a perspective for exploring targeted therapy of tumor cells and tumor microenvironment, and offering a promising clinical strategy for the treatment of retinoblastoma.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"621-631"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}