AAPS PharmSciTech最新文献

{"title":"Engineering Next-generation Drug Delivery Systems Via 4-D Printing: A Paradigm Shift Toward Precision Medicine.","authors":"Charmi Dudhat, Shruti Rawal, Mohit Shah, Riya Patel","doi":"10.1208/s12249-026-03532-1","DOIUrl":"https://doi.org/10.1208/s12249-026-03532-1","url":null,"abstract":"<p><p>Four-dimensional (4-D) printed constructs have recently become clinically relevant platforms for customized and precise drug delivery due to their bio-programmability, bio-responsiveness, and spatiotemporal transformative potential. The 4-DP bio-constructs are highly bio-interactive and dynamically evolving as per therapeutic requisite. In this review, we aim to provide a detailed discourse on the key mechanisms that drive 4-D transformations of a broad spectrum of materials-ranging from shape-memory (SM) systems, liquid crystalline elastomers (LCEs), self-healing and multi-responsive polymers, metamaterials, and select bio-derived materials. The review also summarizes various conventional and advanced additive manufacturing strategies that have been employed for 4-DP of various bio-constructs. Contemporary representatives of various 4-DP drug delivery devices such as smart hydrogels and scaffolds, implants, stents, prosthetics, microneedles, responsive biomedical devices, and dynamic organ- and tumor-on-chip platforms have also been highlighted. Characterization methodologies, preclinical considerations, translational challenges, and the evolving patent and industrial landscape have also been recapitulated. The review also intends to provide critical perspectives on the expanding horizons and translational glitches of 4-DP while elucidating the key bottlenecks to its commercial large-scale integration and clinical translation.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890644","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":"Advanced Bisoprolol Oral Liquid Formulations for Flexible Pediatric and Geriatric Pharmacotherapy.","authors":"María Alejandra Operto, Marina Antonio, Rubén Maggio, Darío Leonardi, Silvana Vignaduzzo","doi":"10.1208/s12249-026-03520-5","DOIUrl":"https://doi.org/10.1208/s12249-026-03520-5","url":null,"abstract":"<p><p>The increasing demand for oral liquid formulations (OLFs), highlights the need to optimize pharmacotherapy in pediatric and geriatric populations, where swallowing difficulties and dose individualization are critical. One such drug is bisoprolol, a highly selective β1-adrenergic receptor blocker widely used in the management of cardiovascular diseases, for which individualized dose titration is frequently required, particularly in pediatric and geriatric patients. Conventional solid dosage forms often lack the flexibility required, potentially compromising adherence and increasing the risk of medication errors. This study aimed to develop safe, stable, and palatable OLFs of bisoprolol fumarate suitable for individualized dosing. A Quality by Design (QbD)-oriented approach was employed to define the Quality Target Product Profile (QTPP) and identify Critical Quality Attributes (CQAs), including drug content, pH, and organoleptic properties. Two sets of formulations were prepared: sugar-free drops and syrups, each at two strengths (2.5 and 5.0 mg mL^-1). Physical, chemical, and microbiological stability were assessed over 12 months under long-term (4 °C and 25 °C) and 6 months under accelerated conditions (40 °C), using a validated methodology. All formulations remained within predefined specifications, showing no significant degradation or physicochemical changes. Microbiological quality and palatability were maintained throughout the study. These findings demonstrate that the strategy based on QbD principles enables the development of robust, patient-centric OLFs, representing a reliable alternative to extemporaneous preparations and supporting safer, more flexible cardiovascular therapy.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890738","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":"Novel Hybrid Polymer-Lipid-Based Formulations for Enhanced Dissolution Rates of Poorly Water-Soluble Drugs: A Quality by Design (QbD) Approach via Hot Melt Extrusion.","authors":"Siva S Kolipaka, Laura A Junqueira, Vivek Garg, Shaumil Bhatt, Vivek Trivedi, Dennis Douroumis","doi":"10.1208/s12249-026-03530-3","DOIUrl":"https://doi.org/10.1208/s12249-026-03530-3","url":null,"abstract":"<p><p>This study presents a Quality by Design (QbD) strategy combined with Design of Experiments (DoE) to develop hybrid polymer-lipid hot-melt extruded (HME) formulations aimed at improving the dissolution rate and palatability of ibuprofen (IBU), a Biopharmaceutics Classification System (BCS) Class II drug with poor aqueous solubility. A fractional factorial design was applied to evaluate the influence of Eudragit EPO and Gelucire 48/16 (GLC) ratios on the preparation of IBU-loaded extrudates. Physicochemical characterisation of the micronised extrudates, using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD), confirmed the formation of amorphous solid dispersions (98.0-99.8%). The DoE analysis demonstrated that the EPO/GLC ratio significantly affected crystallinity, particle size distribution, and dissolution performance. The optimised hybrid polymer-lipid formulations exhibited immediate drug release (> 80%) within 45 min. Furthermore, in vivo evaluation indicated effective taste masking and improved palatability.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890705","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":"Regulatory and Quality Considerations of Antibody-drug Conjugates.","authors":"Karen J Cha, Morris Rosenberg","doi":"10.1208/s12249-026-03503-6","DOIUrl":"https://doi.org/10.1208/s12249-026-03503-6","url":null,"abstract":"<p><p>Antibody-Drug Conjugates (ADCs) have become well-established as an important class of oncology therapeutics with 15 FDA-approved ADCs for various cancer types and hundreds more ADCs in clinical development. This chapter highlights the unique regulatory considerations for the development of ADCs in oncology given their dual nature as biologics and small-molecule drugs. Topics covered include the organization of applications in eCTD format, meeting types with FDA, and key considerations for a successful regulatory application with a particular emphasis on the Chemistry, Manufacturing, and Controls (CMC)-related strategy. Regulatory pathways, such as Fast Track and Breakthrough Therapy, are discussed as options to expedite ADC development. In early development, both the antibody and the cytotoxic linker-payload must meet detailed CMC requirements to ensure patient safety. The transition from a Phase 1-enabling process to a validated, commercial-scale manufacturing process for a biologic involves a complex interplay of science, engineering, and regulatory compliance. This transition is often on the critical path, particularly as many novel biologic therapies receive Fast Track and/or Breakthrough Therapy Designation. This paper outlines the critical steps in process development and scale-up, highlighting common gaps encountered when moving from an early-stage process with limited manufacturing experience to a fully validated commercial process. By providing a comprehensive overview of the required regulatory deliverables and a roadmap for sequencing key workstreams, this paper aims to guide readers through the essential steps and potential pitfalls in advancing a biologic therapy from early clinical development to market launch.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890471","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":"Formulation, Optimization and Characterization of Acetazolamide-Loaded Solid Lipid Nanoparticles for Glaucoma Treatment: In-Vitro and In-Vivo Study.","authors":"Shuchi Goyal, Ankur, Garima, Rajan Swami, Neeraj Mittal","doi":"10.1208/s12249-026-03538-9","DOIUrl":"https://doi.org/10.1208/s12249-026-03538-9","url":null,"abstract":"<p><p>The goal of the present study is to optimize acetazolamide-loaded solid lipid nanoparticles (AZM-loaded SLNs) using central composite design (CCD) for prolonged ocular delivery. The emulsion solvent evaporation process was used to develop AZM-loaded SLNs. The optimal formulation parameters influencing particle size, entrapment efficiency, and percentage drug release were determined using a CCD, and the effects of these variables on the formulation were examined. Furthermore, the particle size, entrapment effectiveness, and in-vitro drug release were carried out, along with FTIR, XRD, DSC, SEM, and TEM, which were used to determine structural and physicochemical properties. The ex-vivo corneal permeability investigations were used to assess drug penetration, and in-vivo experiments in rabbit eyes were conducted to assess the impact on reducing intraocular pressure. Moreover, hemocompatibility, sterility, and eye irritation were also used to evaluate the formulation's safety features. The optimized AZM-loaded SLNs had a drug entrapment efficiency of 89.45%, a particle size of 110.3 nm, and a prolonged drug release of 87.76% in a 24 h period. The drug's effective incorporation into the lipid carrier particles was verified by FTIR, XRD, DSC, SEM, and TEM. Ex-vivo corneal permeation showed that it was significantly higher than both the pure drug and the marketed formulation. Additionally, the in-vivo studies showed a reduction in the intraocular pressure (IOP) during 24 h. A promising nanocarrier system for prolonged ocular administration and better glaucoma patient management has been represented by the developed AZM-loaded SLNs.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890672","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":"Quality by Design for Bilayer Tablets: Integrating Formulation, Manufacturing, and Process Analytical Technology.","authors":"Joao D Simão, António J Ribeiro","doi":"10.1208/s12249-026-03535-y","DOIUrl":"https://doi.org/10.1208/s12249-026-03535-y","url":null,"abstract":"<p><p>Bilayer fixed-dose combination tablets are increasingly used to improve adherence and tailor drug-release profiles, but their development remains challenging because multiple interacting formulation and process variables strongly affect product performance. Quality by Design (QbD) offers a systematic framework to address these challenges, yet its implementation for bilayer tablets and associated analytical methods remains fragmented. In this review we map and critically analyze published applications of QbD to the formulation design, manufacturing process, and testing of bilayer tablets. Using the available literature and regulatory guidance, we summarize the rationale for bilayer formulations, the experimental designs employed, the RA tools used, and the main critical material attributes (CMAs), critical process parameters (CPPs), and critical quality attributes (CQAs) identified. Particular emphasis is placed on the use of design of experiments, process analytical technology, and multivariate data analysis to understand and control mechanical properties, interfacial adhesion, and drug-release behavior, as well as on the current status of analytical QbD for bilayer products. Overall, the evidence shows that QbD has improved control of drug release and interfacial strength and supported the scale-up of bilayer manufacturing, but prior risk analysis, robust control strategies, and Analytical Quality by Design (AQbD)-based dissolution and stability methods are still inconsistently implemented. The concepts and design principles summarized here are expected to support more rational, regulatory-aligned development of bilayer tablets and to guide future QbD applications in this field.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890445","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":"Multi-Omics-Driven Insights into Cancer Biology and Therapeutic Targeting.","authors":"Deval Koshti, Nikhil Khandale, Jignesh Shah, Darshil Shah, Vrashabh V Sugandhi, Dilip Maheshwari, Vishal Shah, Sanyog Jain","doi":"10.1208/s12249-026-03500-9","DOIUrl":"https://doi.org/10.1208/s12249-026-03500-9","url":null,"abstract":"<p><p>The increasing biological complexity and heterogeneity of cancer have driven a shift in oncology drug discovery from single-target approaches toward system-level strategies capable of capturing multilayered disease regulation. Multi-omics technologies, including genomics, transcriptomics, proteomics, metabolomics, epigenomics, and microbiomics, have emerged as powerful tools for elucidating cancer-driving mechanisms, identifying therapeutic targets, and enabling biomarker-guided drug development. This review examines how integrative multi-omics approaches support cancer drug discovery and therapeutic targeting, focusing on target identification, pathway elucidation, target validation, biomarker discovery, and therapeutic development. Genomics and transcriptomics facilitate the identification of driver alterations and dysregulated signaling pathways, whereas proteomics and metabolomics provide functional insights into protein activity, metabolic reprogramming, and treatment response. We further highlight the contributions of epigenomic and microbiomic profiling to biomarker discovery, therapeutic response prediction, and precision oncology. Given the complexity of multi-omics datasets, the review also explores the application of artificial intelligence (AI) and machine-learning methodologies for data integration, network modeling, biomarker discovery, and drug repurposing, including deep learning, Bayesian frameworks, graph-based models, and explainable AI approaches. Emerging computational frameworks and integration strategies that enable interpretation of heterogeneous molecular datasets and support therapeutic discovery are also discussed. Cancer-focused examples demonstrate how integrative multi-omics frameworks have enabled the identification of clinically relevant biomarkers, therapeutic targets, and rational combination therapies. Furthermore, the clinical translation of biomarker-driven precision oncology, exemplified by HER2-, EGFR-, and MSI-directed therapies, highlights the growing impact of omics-informed approaches on personalized cancer treatment. Overall, AI-enabled multi-omics approaches hold substantial promise for accelerating cancer drug discovery and precision oncology.</p>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863386","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":"Polymeric Azelaic Acid-loaded Nanocapsules Incorporated into Tragacanth Gum: Development and Biological Evaluation in Alternative Models for the Treatment of Rosacea","authors":"Tainara Benin,&nbsp;Graziela Scheuer Gomes,&nbsp;Eduarda Cristina Jacobus Ferreira,&nbsp;Victor de Mello Palma,&nbsp;Aline de Cristo Soares Alves,&nbsp;Fernanda Visioli,&nbsp;Adriana Raffin Pohlmann,&nbsp;Silvia Stanisçuaski Guterres,&nbsp;Luiza Abrahão Frank","doi":"10.1208/s12249-026-03476-6","DOIUrl":"10.1208/s12249-026-03476-6","url":null,"abstract":"<div><p>Rosacea is an inflammatory skin disorder that significantly impairs patients’ quality of life. Azelaic acid (AZA), a well-established keratolytic and anti-inflammatory agent; however, its clinical application is often limited by local adverse effects that reduce patient adherence. In this context, nanotechnology-based drug delivery systems, particularly polymeric nanocapsules, represent a promising strategy to improve physicochemical stability, reduce cutaneous irritation, and enable incorporation into semi-solid formulations with enhanced skin interaction. This study aimed to develop and characterize AZA-loaded polymeric nanocapsules incorporated into tragacanth gum–based hydrogels as a safe, effective, and patient-friendly therapeutic alternative for rosacea. The nanocapsules exhibited a uniform nanometric size (185.66 ± 2.08 nm), low polydispersity index (0.12 ± 0.02), slightly negative zeta potential (− 8.67 ± 0.26 mV), and a skin-compatible acidic pH (3.56 ± 0.16). Drug loading reached 0.53 mg/mL, with an encapsulation efficiency of 42.20%. <i>In vitro</i> cytocompatibility assays showed cell viability close to 100% after 12 and 24 h of exposure, confirming the safety of the system. Antiangiogenic assays using chicken embryos further supported its biocompatibility. The hydrogels displayed a slightly acidic pH and pseudoplastic flow behavior described by the Herschel–Bulkley model, along with higher adhesiveness than liquid suspensions, favoring topical application. Both conventional AZA hydrogels (TG-AZA) and nanocapsule-based hydrogels (TG-NC-AZA) promoted effective drug retention within the stratum corneum. Notably, TG-NC-AZA showed a non-irritant profile in HET-CAM and CAM-TBS assays and demonstrated pronounced anti-inflammatory activity, achieving a 75% reduction. Overall, these findings highlight TG-NC-AZA as an innovative and clinically relevant therapeutic approach for rosacea.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03476-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148782524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Benzene-Free Carbomer 980 in the Formulation of Metronidazole Gel 0.75% and Demonstration of Equivalence with Carbomer 940","authors":"Om Sambhaji Shelke,&nbsp;Jie Feng,&nbsp;Zhong Liu,&nbsp;Yulan Chen,&nbsp;Yijie Zhu,&nbsp;Zheng Zhang","doi":"10.1208/s12249-026-03487-3","DOIUrl":"10.1208/s12249-026-03487-3","url":null,"abstract":"<div><p>The U.S. FDA currently recommends avoiding carbomer grades that contain benzene and recommends benzene-free alternatives (USFDA. Guidance for Industry: reformulating drug products that contain carbomers manufactured with benzene. Center for Drug Evaluation and Research (CDER), Pharmaceutical Quality/CMC. Published in December 2023. Available at: https://www.fda.gov/media/175083/download). This means that if a finished product is authorized with a carbomer grade containing benzene, it needs to be replaced with a non-benzene carbomer grade. Such an update would also require detailed comparative studies—covering structure, performance, stability, and biological equivalence—to confirm consistent product quality and effectiveness. The current study attempted to replace Carbomer 940 (C940) with Carbomer 980 (C980) in 0.75% Metronidazole Gel. The two carbomer grades were characterized as powders using multiple spectroscopic techniques. A method for analyzing carboxylic acid content was developed and validated, using light-scattering resonance technology to improve accuracy. The formulation prepared with C940 and C980 was characterized for rheology, <i>in vitro</i> release and permeation, and stability, along with the reference formulation. Powder characterization shows slight differences in the absorption spectra across NMR and FTIR studies, while NIR spectra are the same. Additionally, C980 has a slightly higher molecular weight, degree of polymerization, apparent viscosity, and carboxylic acid content, but a lower water loss. The formulations prepared with C940 and C980 are rheologically equivalent to the reference formulation as assessed by flow curves, yield stress, linear viscoelasticity, and creep. The <i>in vitro</i> release and permeation study also demonstrates that the formulations prepared with C940 and C980 exhibit performance equivalence to the innovator formulation under the tested conditions. Hence, replacing the benzene-grade carbomer with the corresponding non-benzene-grade carbomer does not significantly affect product performance relative to the reference product.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148710917","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":"Retraction Note: Nasal In-Situ Gels of Brij®-Enriched Novasomes as Optimistic Nanovesicular Carriers for Enhancing Anti-Depressant Action of Agomelatine","authors":"Tarek M. Ibrahim,&nbsp;Ayman M. Fathi,&nbsp;Nourhan A. Abdulla","doi":"10.1208/s12249-026-03501-8","DOIUrl":"10.1208/s12249-026-03501-8","url":null,"abstract":"","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"27 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1208/s12249-026-03501-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148552984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}