Results in pharma sciences最新文献

{"title":"Development and characterization of in-situ gel for ophthalmic formulation containing ciprofloxacin hydrochloride","authors":"S.B. Makwana,&nbsp;V.A. Patel,&nbsp;S.J. Parmar","doi":"10.1016/j.rinphs.2015.06.001","DOIUrl":"10.1016/j.rinphs.2015.06.001","url":null,"abstract":"<div><p><em>In situ</em> gels are systems which are applied as solutions or suspensions and are capable of undergoing rapid sol-to-gel transformation triggered by external stimulus such as temperature, pH etc. on instillation. The aim of the present study was to formulate and evaluate pH responsive <em>in-situ</em> gel for ophthalmic delivery. Ciprofloxacin hydrochloride is popularly used as a broad spectrum antibiotic in the treatment of corneal ulcers of ocular infections. However, rapid dilution on instillation, wash out, poor retention of drug concentration delimit the therapeutic benefits of the drug when used in form of conventional eye drops. Sodium alginate, an ophthalmic gel forming mucoadhesive polymer was chosen as polymer which undergoes instantaneous gel formation due to formation of calcium alginate by virtue of its interaction with divalent cation (Ca⁺²) present in lachrymal fluid. Hydroxy Propyl Methyl Cellulose (HPMC K4M and E5 0LV) was further incorporated as a viscosity enhancer in order to achieve the desired consistency so as to facilitate sustained drug release. The developed formulations were evaluated for clarity, pH measurement, gelling capacity, drug content, rheological study, and in vitro drug release. Thus, in situ gel based systems containing gums can be a valuable approach for ophthalmic drug delivery when compared to conventional systems.</p></div>","PeriodicalId":89718,"journal":{"name":"Results in pharma sciences","volume":"6 ","pages":"Pages 1-6"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.rinphs.2015.06.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55073717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in the rheological properties and mixing compatibility with heparinoid cream of brand name and generic steroidal ointments: The effects of their surfactants","authors":"Shuji Kitagawa,&nbsp;Reiko Yutani,&nbsp;Rhu-ichi Kodani,&nbsp;Reiko Teraoka","doi":"10.1016/j.rinphs.2016.02.001","DOIUrl":"10.1016/j.rinphs.2016.02.001","url":null,"abstract":"<div><p>Most steroidal ointments contain propylene glycol (PG) and surfactants, which improve the solubility of corticosteroids in white petrolatum. Surfactants aid the uniform dispersal of PG within white petrolatum. Since the surfactants used in generic ointments are usually different from those used in brand name ointments, we investigated the effects of surfactants on the rheological properties of three brand name ointments and six equivalent generic ointments. We detected marked differences in hardness, adhesiveness, and spreadability among the ointments. Further examinations of model ointments consisting of white petrolatum, PG, and surfactants revealed that the abovementioned properties, especially hardness and adhesiveness, were markedly affected by the surfactants. Since steroidal ointments are often admixed with moisturizing creams prior to use, we investigated the mixing compatibility of the ointments with heparinoid cream and how this was affected by their surfactants. We found that the ointments containing glyceryl monostearate demonstrated good mixing compatibility, whereas those containing non-ionic surfactants with polyoxyethylene chains exhibited phase separation. These results were also consistent with the findings for the model ointments, which indicates that the mixing compatibility of steroidal ointments with heparinoid cream is determined by the emulsifying capacity of the surfactants in their oily bases.</p></div>","PeriodicalId":89718,"journal":{"name":"Results in pharma sciences","volume":"6 ","pages":"Pages 7-14"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.rinphs.2016.02.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55073745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzymatic activity in the presence of surfactants commonly used in dissolution media, Part 1: Pepsin","authors":"Maria L Guzman ,&nbsp;Margareth R Marques ,&nbsp;Maria E Olivera ME ,&nbsp;Erika S Stippler","doi":"10.1016/j.rinphs.2016.02.002","DOIUrl":"10.1016/j.rinphs.2016.02.002","url":null,"abstract":"<div><p>The <em>United States Pharmacopeia</em> (<em>USP</em>) General Chapters Dissolution 〈711〉 and Disintegration and Dissolution of Dietary Supplements 〈2040〉 allows the use of enzymes in dissolution media when gelatin capsules do not conform to dissolution specifications due to cross linking. Possible interactions between enzymes and surfactants when used together in dissolution media could result in loss of the enzymatic activity. Pepsin is an enzyme commonly used in dissolution media, and in this work, the activity of pepsin was determined in the presence of different surfactants as usually found in case of dissolution tests of certain gelatin capsule formulations.</p><p>Pepsin enzymatic activity was determined according to the <em>Ninth Edition of the Food Chemicals Codex</em> (<em>FCC</em>) 9 method, in dissolution conditions: simulated gastric fluid, 37<!--> <!-->°C and 50<!--> <!-->rpm. Sodium dodecyl sulfate (SDS), cetyltrimethyl ammonium bromide (CTAB), polysorbate 80 (Tween 80) and octoxynol 9 (Triton X100) in concentrations above and below their critical micellar concentrations were selected. Results showed a significant reduction in the activity of pepsin at all the concentrations of SDS assayed. On the contrary, CTAB, Tween 80, and Triton X100 did not alter the enzymatic activity at of pepsin any of the concentration assayed.</p><p>This data demonstrates a rational selection of the surfactant to be used when pepsin is required in dissolution test.</p></div>","PeriodicalId":89718,"journal":{"name":"Results in pharma sciences","volume":"6 ","pages":"Pages 15-19"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.rinphs.2016.02.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55073762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of binder moisture content in Metformin HCL high-dose formulations prepared by moist aqueous granulation (MAG)","authors":"Hiroshi Takasaki ,&nbsp;Etsuo Yonemochi ,&nbsp;Masanori Ito ,&nbsp;Koichi Wada ,&nbsp;Katsuhide Terada","doi":"10.1016/j.rinphs.2015.09.001","DOIUrl":"10.1016/j.rinphs.2015.09.001","url":null,"abstract":"<div><p>The aim of this study was to evaluate binders to improve the flowability of granulates and compactibility of Metformin HCL (Met) using the moist aqueous granulation (MAG) process. The effect of the binder moisture content on granulate and tablet quality was also evaluated. Vinylpyrrolidone–vinyl acetate copolymer (Kollidon VA64 fine: VA64), polyvidone (Povidone K12: PVP), hydroxypropyl cellulose (HPC SSL SF: HPC) and hydroxypropyl methylcellulose (Methocel E5 LV: HPMC) were evaluated as binders. These granulates, except for HPMC, had a lower yield pressure than Met active pharmaceutical ingredient (API). HPMC Met was not sufficiently granulated with low water volume. No problems were observed with the VA64 Met granulates during the tableting process. However, HPC Met granulates had a bowl-forming tendency, and PVP Met granulates had the tendency to stick during the tableting process. These bowl-forming and sticking tendencies may have been due to the low moisture absorbency of HPC and the high volume of bound water of PVP, respectively. VA64 Met granulates had the highest ambient moisture content (bulk water, bound water) and moisture absorbency. It was concluded that the type of binder used for the Met MAG process has an impact on granulate flow and compactibility, as well as moisture absorbency and maintenance of moisture balance.</p></div>","PeriodicalId":89718,"journal":{"name":"Results in pharma sciences","volume":"5 ","pages":"Pages 1-7"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.rinphs.2015.09.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55073733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advisory Board","authors":"","doi":"10.1016/S2211-2863(14)00008-6","DOIUrl":"https://doi.org/10.1016/S2211-2863(14)00008-6","url":null,"abstract":"","PeriodicalId":89718,"journal":{"name":"Results in pharma sciences","volume":"4 ","pages":"Page i"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S2211-2863(14)00008-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137223684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological conversion of aripiprazole lauroxil − An N-acyloxymethyl aripiprazole prodrug","authors":"Morten Rohde ,&nbsp;Niels M∅rk ,&nbsp;Anders E. Håkansson ,&nbsp;Klaus G. Jensen ,&nbsp;Henrik Pedersen ,&nbsp;Tina Dige ,&nbsp;Erling B. J∅rgensen ,&nbsp;René Holm","doi":"10.1016/j.rinphs.2014.04.002","DOIUrl":"10.1016/j.rinphs.2014.04.002","url":null,"abstract":"<div><p><em>N</em>-acyloxyalkylation of <em>NH</em>-acidic compounds can be a prodrug approach for e.g. tertiary or some <em>N</em>-heterocyclic amines and secondary amides and have the potential to modify the properties of the parent drug for specific uses, for example its physicochemical, pharmacokinetic or biopharmaceutical properties. Aripiprazole lauroxil was prepared as a model compound for such prodrugs and its bioconversion was investigated both <em>in vitro</em> and <em>in vivo</em>. Theoretically, <em>N</em>-acyloxyalkyl derivates of <em>NH</em>-acid compounds undergo a two-step bioconversion into the parent <em>NH</em>-acidic drug through an <em>N</em>-hydroxyalkyl intermediate. However, to our knowledge no published studies have investigated the formation of an intermediate <em>in vivo</em>. In the present study, it was demonstrated that the assumed <em>N-</em>hydroxymethyl intermediate was readily observed both <em>in vitro</em> and <em>in vivo</em>. <em>In vivo</em>, the observed plasma concentration of the intermediate was at the same level as the drug (aripiprazole). When prodrug intermediates are formed, it is important to make a proper pharmacological, pharmacokinetic and toxicological evaluation of the intermediates to ensure patient safety; however, several challenges were identified when testing an <em>N</em>-acyloxyalkyl prodrug. These included the development of a suitable bioanalytical method, the accurate prediction of prodrug bioconversion and thereby the related pharmacokinetics in humans and the toxicological potential of the intermediate.</p></div>","PeriodicalId":89718,"journal":{"name":"Results in pharma sciences","volume":"4 ","pages":"Pages 19-25"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.rinphs.2014.04.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33117041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of formulation properties and skin penetration in the same additive-containing formulation","authors":"Yutaka Inoue ,&nbsp;Kensuke Suzuki ,&nbsp;Rikimaru Maeda ,&nbsp;Arisa Shimura ,&nbsp;Isamu Murata ,&nbsp;Ikuo Kanamoto","doi":"10.1016/j.rinphs.2014.09.003","DOIUrl":"10.1016/j.rinphs.2014.09.003","url":null,"abstract":"<div><p>The aim of this study is to examine the physicochemical properties of the external preparation, the effect on the skin permeability and the human senses. Miconazole nitrate cream formulation (MCZ-A: bland name and MCZ-B, −C, −D: generics) to measure the physicochemical properties, was performed by the skin permeation test and human sensory test. The flattening, viscoelasticity, and water content of each cream were measured and each cream was subjected to near-infrared (NIR) absorption spectroscopy and human sensory testing. The yield value was calculated based on measured flattening and was 734.8<!--> <!-->dynes/cm² for MCZ-A, 1198.9<!--> <!-->dynes/cm² for MCZ-B, 461.3<!--> <!-->dynes/cm² for MCZ-C and 3112.3<!--> <!-->dynes/cm² for MCZ-D. Measurement of viscoelasticity and viscosity revealed that MCZ-C had a smaller tanδ than the other 3 creams at 25<!--> <!-->°C. NIR absorption spectroscopy revealed that MCZ-A had the highest absorption peak due to hydroxyl groups, followed by MCZ-C, −B, and then −D. Measurement of water content revealed that MCZ-A had a water content of 65.9%, MCZ-B, −C, and −D had a water content of around 56.3%. Human sensory testing revealed differences between MCZ-A and MCZ-C and between MCZ-B and MCZ-D in terms of spreadability and feel. These findings indicate that differences in water and oil content and emulsification resulted in the creams having different physical properties, such as flattening, internal structure, and dynamic viscoelasticity. NIR absorption spectroscopy, which allows non-destructive measurement of a sample’s physicochemical properties, and measurement of viscoelasticity and viscosity, which allows measurement of a sample’s dynamic viscoelasticity, revealed differences in the physical properties of creams. The skin permeation test, skin MCZ amount was 7.48<!--> <!-->µg/cm² for MCZ-A, 5.11<!--> <!-->µg/cm² for MCZ-B, 12.08<!--> <!-->µg/cm² for MCZ-C and 3.75<!--> <!-->µg/cm² for MCZ-D. In addition, since the drug spread is good about the skin migration, spreadability is affecting the potential dermal transfer.</p></div>","PeriodicalId":89718,"journal":{"name":"Results in pharma sciences","volume":"4 ","pages":"Pages 42-49"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.rinphs.2014.09.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33117044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of poly (ethylene glycol)-coated perfluorodecalin-filled poly (lactide-co-glycolide) microcapsules following intravenous administration of high amounts in rats","authors":"Katja B. Ferenz ,&nbsp;Indra N. Waack ,&nbsp;Julia Laudien ,&nbsp;Christian Mayer ,&nbsp;Martina Broecker-Preuss ,&nbsp;Herbert de Groot ,&nbsp;Michael Kirsch","doi":"10.1016/j.rinphs.2014.04.001","DOIUrl":"10.1016/j.rinphs.2014.04.001","url":null,"abstract":"<div><p>The host response against foreign materials designates the biocompatibility of intravenously administered microcapsules and thus, widely affects their potential for subsequent clinical use as artificial oxygen/drug carriers. Therefore, body distribution and systemic parameters, as well as markers of inflammation and indicators of organ damage were carefully evaluated after administration of short-chained poly (vinyl alcohol, (PVA)) solution or poly (ethylene glycol (PEG))-shielded perfluorodecalin-filled poly (<span>d</span>,<span>l</span>-lactide-co-glycolide, PFD-filled PLGA) microcapsules into Wistar rats. Whereas PVA infusion was well tolerated, all animals survived the selected dose of 1247 mg microcapsules/kg body weight but showed marked toxicity (increased enzyme activities, rising pro-inflammatory cytokines and complement factors) and developed a mild metabolic acidosis. The observed hypotension emerging immediately after start of capsule infusion was transient and mean arterial blood pressure restored to baseline within 70 min. Microcapsules accumulated in spleen and liver (but not in other organs) and partly occluded hepatic microcirculation reducing sinusoidal perfusion rate by about 20%.</p><p>Intravenous infusion of high amounts of PFD-filled PLGA microcapsules was tolerated temporarily but associated with severe side effects such as hypotension and organ damage. Short-chained PVA displays excellent biocompatibility and thus, can be utilized as emulsifier for the preparation of drug carriers designed for intravenous use.</p></div>","PeriodicalId":89718,"journal":{"name":"Results in pharma sciences","volume":"4 ","pages":"Pages 8-18"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.rinphs.2014.04.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33117040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of an alternative disturbed skin model by mechanical abrasion to study drug penetration","authors":"P. Schlupp,&nbsp;M. Weber,&nbsp;T. Schmidts,&nbsp;K. Geiger,&nbsp;F. Runkel","doi":"10.1016/j.rinphs.2014.09.002","DOIUrl":"10.1016/j.rinphs.2014.09.002","url":null,"abstract":"<div><p>Pharmaceuticals and cosmetics for dermal application are usually tested on healthy skin, although the primary permeation barrier, the stratum corneum, is often impaired by skin diseases or small skin lesions, especially on the hands. These skin conditions can considerably influence the permeation of chemicals and drugs. Furthermore, risk assessment for example of nanoparticles should be performed under various skin conditions to reflect the true circumstances. Therefore, an alternative and reproducible method for a high throughput of skin samples with impaired skin barrier was developed and verified by skin permeation studies (25<!--> <!-->h) of caffeine, sorbic acid and testosterone compared to healthy (untreated) and tape-stripped skin. Skin barrier disruption was controlled by <em>TEWL</em> measurement.</p><p>Skin permeation of the three substances was increased in tape-stripped and abraded skin compared to untreated skin due to the reduced barrier integrity. Enhancement of drug uptake was highest for the most hydrophilic substance, caffeine, followed by sorbic acid and lipophilic testosterone. No significant difference in drug uptake studies was observed between the new abrasion method with an aluminum-coated sponge and the tape-stripping method. The obtained results demonstrate that this abrasion method is an alternative way to achieve a disturbed skin barrier for drug and chemical uptake studies.</p></div>","PeriodicalId":89718,"journal":{"name":"Results in pharma sciences","volume":"4 ","pages":"Pages 26-33"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.rinphs.2014.09.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33117042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of the excipient concentration on the pharmacokinetics of PM181104, a novel antimicrobial thiazolyl cyclic peptide antibiotic, following intravenous administration to mice","authors":"Vijayaphanikumar Yemparala,&nbsp;Anagha A. Damre,&nbsp;Venkat Manohar,&nbsp;Kishori Sharan Singh,&nbsp;Girish B. Mahajan,&nbsp;Satish N. Sawant,&nbsp;Tanaji Deokule,&nbsp;H. Sivaramakrishnan","doi":"10.1016/j.rinphs.2014.09.001","DOIUrl":"10.1016/j.rinphs.2014.09.001","url":null,"abstract":"<div><p>Thiazolyl cyclic peptide antibiotics are known for their poor aqueous solubility and unfavorable pharmacokinetics (PK) and hence pose challenging tasks in developing these antibiotics as clinical candidates. In the current paper, we report a possible way to address these challenges with exemplification of our antibiotic PM181104. The approach was to prepare formulations with known excipients, Polysorbate 80 (Tween 80, T-80) and PEG 400 through their varied stiochiometric combination in appropriate ratio to achieve acceptable osmolarity, pH and particle size of the formulation. Two different sets of formulations were prepared with two distinct average particle diameters ranging from 32.8 to 465.4<!--> <!-->nm. First, semi-transparent solutions with a particle size of &gt;100<!--> <!-->nm were achieved by keeping concentration of PEG 400 constant at 8% (w/v) and decreasing the amounts of T-80. Second, clear colorless solutions with a particle size of &lt;100<!--> <!-->nm were achieved by keeping concentration of T-80 constant at 8% (w/v) and decreasing the amounts of PEG 400. In PK studies, intravenous administration of formulation with particle size &lt;100<!--> <!-->nm to mice resulted in a two-fold increase in area under the plasma concentration-time curve (AUC_last) and concentration at time zero (<em>C</em>₀), there by facilitating the selection of suitable formulation for further efficacy studies.</p></div>","PeriodicalId":89718,"journal":{"name":"Results in pharma sciences","volume":"4 ","pages":"Pages 34-41"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.rinphs.2014.09.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33117043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}