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@#Population bioequivalence (PBE) is a statistical approach recommended by FDA to evaluate the consistency of particle size distribution of numerous nanoparticle products.However, when particle size distribution (PSD) profile exhibits multiple peaks or other complex distributions, the traditional descriptors D50 and SPAN are no longer suitable to describe PSD.Earth mover''s distance (EMD) is a new statistical metric for assessing the difference between distributions.In this study, we used EMD to measure the discrepancy between PSD and then PBE was applied to perform statistical test to establish equivalence.Our results showed that the proposed method can effectively reject an unequivalent product and pass an equivalent product, thus indicating its helpfulness in guiding the optimization of formulation and preparation process.
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Objective:To study the extraction method and characteristics of vesicle-like nanoparticles （VLNs） in Astragali Radix decoction， and to explore the mechanism of the VLNs in reducing blood glucose by regulating the gut microbiota of db/db diabetic mice. Method:Ultracentrifugation and size exclusion chromatography were used to enrich VLNs from Astragali Radix decoction， and the morphology， particle size and concentration of the VLNs were analyzed by transmission electron microscope and nanoparticle tracking analyzer. The db/db diabetic mice were randomly divided into model group， Astragali Radix VLNs high-， medium- and low-dose （21.1， 10.6， 5.3 g·kg<sup>-1</sup>） groups and metformin group （0.25 g·kg<sup>-1</sup>） according to their blood glucose levels. There were 7 mice in each group， and another 7 C57BL/6 mice were set as the normal group. The mice were given intragastrically for 3 weeks （once a day）， and the changes of fasting blood glucose were observed every week. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology of liver and pancreas of diabetic mice. The feces of mice were collected for 16S rRNA diversity detection of intestinal microbes. Result:The size of the nanoparticles obtained by the two methods was about 200 nm. Astragali Radix VLNs extracted by ultracentrifugation had a typical saucer-like shape with the concentration of 3.0×10<sup>11</sup> particles·mL<sup>-1</sup>. The morphology of Astragali Radix VLNs obtained by size exclusion chromatography was relatively poor with the concentration of 2.2×10<sup>11</sup> particles·mL<sup>-1</sup>. After 3 weeks of administration， compared with the model group， Astragali Radix VLNs high-， medium- and low-dose groups could significantly reduce the fasting blood glucose of diabetic mice （<italic>P</italic><0.05， <italic>P</italic><0.01）. The VLNs could improve the gut microbiota dysbiosis， significantly decrease the ratio of Firmicutes/Bacteroidota， and increase the relative abundance of beneficial bacteria and reduce the relative abundance of harmful bacteria. Conclusion:Astragali Radix VLNs may reduce the blood glucose of db/db diabetic mice by adjusting the ratio of Firmicutes/Bacteroidota in the intestinal flora.
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ABSTRACT: This study evaluated the effects of the physically effective fiber (peNDF) content on nutrient composition of the total mixed ration (TMR), orts and fecal parameters in 15 commercial beef feedlots. The particle size distribution of TMR was measured adopting Penn State Particle Size Separator (PSPS). Samples were evaluated for dry matter (DM), ash, ether extract (EE), crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF) and starch content. Fecal samples were also evaluated for pH and score. The feedlots were categorized into peNDF<20% and peNDF ≥ 20%. Data were analyzed by a model that included fixed effects of treatment and covariates (sex and genetic groups). Levels of DM, CP, EE and starch were lower in TMR with peNDF ≥ 20% (P<0.05). Fecal dry matter was higher and morning fecal pH was lower for TMR with peNDF<20% (P<0.05). Physically effective fiber changed nutrient levels in TMR, orts, fecal pH and DM. So, using PSPS and fecal parameters are practical and indirect tools for measuring fecal starch and assessing the effectiveness of the diet supplied to ruminants.
RESUMO: O objetivo desse estudo foi avaliar o teor de fibra fisicamente efetiva (FDNfe) de dietas totais e seus efeitos nos nutrientes da dieta, das sobras e nos parâmetros fecais de bovinos de corte em 15 confinamentos comerciais. As amostras da dieta foram separadas utilizando a peneira Penn State Particle Size Separator (PSPS). As amostras foram analisadas quanto aos teores de matéria seca (MS), matéria mineral (MM), extrato etéreo (EE), proteína bruta (PB), fibra em detergente neutro (FDN), fibra em detergente ácido (FDA) e amido. Nas amostras de fezes também foram avaliadas o escore e pH fecal. Os confinamentos foram categorizados em dois tratamentos: FDNfe<20% e FDNfe≥20%. Os dados foram analisados por um modelo que incluiu os efeitos de grupo e covariável (sexo e grupo genético). Os teores de MS, PB, EE e amido foram menores nas dietas com FDNfe≥20%(P<0,05). A MS fecal foi maior e pH fecal matinal foi menor nas dietas com FDNfe<20% (P<0,05). Sendo assim a efetividade da fibra alterou os nutrientes da dieta total e sobras, bem como as variáveis pH e MS fecal. Com isso, o uso de PSPS e parâmetros fecais são ferramentas práticas e indiretas para medir o amido fecal e a efetividade da dieta em confinamentos de bovinos comerciais.
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RESUMO Neste artigo, buscou-se avaliar a sensibilidade da função contínua de distribuição de tamanho de partículas (DTP) diante da modificação decorrente da floculação. Para tal, foram investigadas seis configurações discretas, subdivididas em 3, 4, 5, 6, 7, 8, 10 e 15 classes de tamanho. As configurações investigadas diferem na frequência de partículas presentes por faixa de tamanho e no comportamento, sendo este monotônico ou unimodal. O ajuste da função contínua na forma linearizada aos dados discretos foi avaliado por meio do coeficiente de determinação (R2). O coeficiente de potência da função (β) e o centro de massa (C.M) da distribuição foram tomados como representativos da DTP para a análise de sensibilidade, realizada por meio do estudo da correlação múltipla entre as variáveis. Experimentos em escala de bancada foram conduzidos visando a avaliar a simulação. Os resultados demonstraram que os parâmetros β e C.M foram sensíveis às variações da DTP, todavia os ajustes das funções para distribuições unimodais carecem de aprimoramento.
ABSTRACT In this paper, the sensitivity of the continuous particle size distribution function (PSD) was evaluated, as flocculation occurs. To this end, six discrete configurations were investigated, subdivided into 3, 4, 5, 6, 7, 8, 10 and 15 classes. The distribution studied here differ in the particles presented by size range and behavior, whether monotonic or unimodal. The adjustment of the continuous function in linearized form to the discrete data was evaluated by means of R2. The power law coefficient (β) and the center of mass (C.M) were taken as representative of PSD during the sensitivity analysis, which was carried out by means of multiple correlation between the variables. Batch essays were performed in order to evaluate simulations. Results showed that β and C.M were both sensitive to PSD variations; however, the function adjustments for unimodal distributions need improvement.
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The particle diameters of active pharmaceutical ingredient (API) and excipients are important factors to the quality of preparations and have great significances in the reverse engineering to brand products and the consistent evaluation of generic drugs. In this study, a novel method was established for particle size determination to identify the selected component and eliminate other interferential particles by comparing the microscopic images before and after fusion caused by controllable heating. Stearic acid (SA) particles in irregular and spherical shape were selected as a typical excipient to demonstrate the methodology, which were identified from the mixed particles based upon its melting characteristics to detect their particle sizes as well as the size distributions. In the same approach, the morphology and particle size of fenofibrate particles as API in tablets were analyzed. The results illustrated that the particle diameters and particle size distributions of the selected components in the mixture of particles can be detected via the hot-melting characteristics under the prerequisite of proper pretreatment to separate selected components from other particles in microscopic field. In conclusion, this research provides a practical approach for the reverse engineering purpose to brand products and the consistent evaluation of generic drugs.
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OBJECTIVE: To discuss whether the difference in dissolution profile in vitro may cause different bioavailability in vivo and investigate the effects of the key quality parameters of leflunomide on bioavailability. METHODS: Using SANOFI product as the reference preparation and domestic product as the test preparation, the disintegration solution of leflunomide tablets was analyze by Morphologi G3-ID automated measurement to get the paricile size and size distribution of the API; using pH 6.5 FaSSIF solution without adding ox-gall sulfonic acid sodium and lecithin as the dissolution medium, the dissolution and permeation profiles of the reference and test preparations and raw material were compared at 37 ℃ with rotate speed of 150 r•min-1. The influence of quality parameters on the process of API's release and absorption was investigated, then the difference between the reference and test preparations were compared to preliminarily predict the bioavailability and bioequivalence. RESULTS: The particle size Dv(50)of domestic leflunomide tablets was 79.80 μm, while the particle size Dv(50)of the reference product was 17.60 μm; the dissolution rate and penetration rate of the test preparation were about 70% of the reference preparation, the tmax was basically identical,but the ρmax and AUC0-t were lower than the reference preparation. The bioavailability of the test preparation was about 90% of the reference preparation. CONCLUSION: Though the dissolution profile of domestic leflunomide tablets is not identical to the reference preparation, but the two products were predicted to be bioequivalent.
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Objective: To establish a method for the determination of the particle size of nifedipine and study the effect of particle size on the in vitro dissolution behaviors of nifedipine sustained release tablets. Methods: Light scattering was used to study the parti-cle size of nifedipine API. Nifedipine APIs with different particle sizes were prepared by a portable high-speed grinder. The in vitro dis-solution curve of nifedipine sustained released tablets (Ⅰ) was determined by HPLC. The similarity was evaluated using the similarity factor ( f2) with the original drug (trade name: Adalat-L, specification: 10mg) as the reference preparation. Results: The granulo-metric conditions were as follows: the pump speed of laser size analyzer was 1 800 r·min-1, the shading rate was 8%-20% , the bal-ance time was 0 s, the media was 0. 3% Tween 80, and the ultrasonic time was 1 min. The in vitro dissolution of nifedipine sustained released tablets (Ⅰ) showed that the smaller particle size of nifedipine API, the better the dissolution was. As the Dv90 ( the particle size accounting for 90% of the total particle quantity) was reduced from 118. 781 μm to 3. 471 μm, the cumulative dissolution in 0. 25 h of nifedipine sustained released tablets (Ⅰ) increased from 11. 2% to 44. 0% , the similarity factor ( f2) compared with the dis-solution cruve of the original drug increased firstly and then decreased, and f2value was 77 when the Dv90 was 29. 823 μm. Conclu-sion: The in vitro dissolution of nifedipine sustained released tablets is improved remarkably by micronization technology. In order to produce nifedipine sustained released tablets (Ⅰ) with the same bioavailability as the original drug preparation, the particle size of nife-dipine API should be controlled within the range of 15 μm≤Dv90≤45 μm.
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Objective:To establish a laser light scattering method for the determination of the particle size distribution of clostridium butyricum enterococcus triple viable powder and compare the results of the sieving method.Methods:The conditions of laser scattering method were as follows:the vibration sampling rate of 80%,the dispersion pressure of 0.05 MPa,the background and sample scan time of 15 s,the shading of 0.5%-5%,the refractive index of the particles of 1.55,the particle absorption rate of 0.01,and the injection volume of 0.1-0.2 g.The eigenvalues of the particle size distribution were determined,which were the particle size cumulative distribution map of 10%,50% and 90% of the particle size value and the volume average particle diameter D.Results:The RSDs of d(0.1),d(0.5) and d(0.9) were less than 5% in the methodology study.The results of laser light scattering method showed that the particle size of 93.3% samples was below 250 μm,that of 64.2% samples was below 150 μm,that of 51.4% samples was below 125 μm,and that of 31.3% samples was below 90 μm.The results of sieving method showed that the particle size of 96.6% was below 250 μm,that of 46.4% samples was below 150 μm,that of 23.5% samples was below 125 μm,and that of 1.4% samples was below 90 μm.Conclusion:Sieving method and laser light scattering method both can characterize the particle size distribution of the sample.The laser light scattering method is simple,accurate and producible,which is suitable for the particle size control of clostridium butyricum enterococcus triple viable powder.
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OBJECTIVE:To establish the method for the determination of particle size distribution of Budesonide nasal spray, and to analyze the consistency of particle size distribution of spray samples. METHODS:Water was used as dispersant for mixing and dispersing(1800 r/min). The particle sizes [d(0.1),d(0.5),d(0.9)] corresponded to accumulative particle size of 10%,50%and 90%were used as characteristic value. The distribution of granularity was determined by laser scattering method. The consisten-cy of particle size distribution of samples from 2 manufacturers (A,B) were analyzed among different batches or same batch of same manufacturer by SAS 9.3 statistical software. RESULTS:The mean values of d(0.1),d(0.5) and d(0.9) were 3.96 μm, 29.58 μm and 67.10 μm in manufacturer A. The mean values of d(0.1),d(0.5)and d(0.9)were 2.00 μm,7.53 μm and 28.51 μm in manufacturer B. By analysis,there was great difference in particle size of samples from 2 manufacturers. The particle size of the samples from manufacturer A were larger than that of manufacturer B. The consistency among different batches from manufacturer B was better,and the consistency among same batch were all good from 2 manufacturers. CONCLUSIONS:The established meth-od is suitable for particle size distribution of Budesonide nasal spray and the consistency analysis of particle size distribution.
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OBJECTIVE:To study the effects of particle size of ticagrelor crude drug on in vitro dissolution behavior of Ticagre-lor tablets. METHODS:Ticagrelor crude drug and different particle size of ticagrelor powder A,B,C,D,E after smashing for dif-ferent time(15,30,40,60 s)were used to prepare the tablet by wet granulation method. Accumulative in vitro dissolution rate of prepared tablets within 60 min were determined by UV spectrophotometry at 300 nm(using 0.2% tween as medium,paddle meth-od). Using original tablet as reference preparation,the similarity factor(f2)method was used to compare the similarity of dissolu-tion behavior between 5 prepared tablets and original tablet. RESULTS:d(0.9)of powder A,B,C,D,E were 69.181,40.778, 24.805,12.611,3.083 μm,respectively. The corresponding f2 were 27.77,36.79,50.06,67.68,79.99. CONCLUSIONS:The par-ticle size of ticagrelor crude drug is much smaller,and the dissolution behavior of prepared tablet is closer to that of original tablet. The in vitro dissolution rate of Ticagrelor tablets is improved remarkably by micronization technology. In order to produce Ticagre-lor tablets with the same bioavailability as original tablet,particle size of ticagrelor crude drug powder should be controlled with d(0.9)≤20μm.
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RESUMO: Este artigo apresenta algumas considerações sobre a floculação a partir da análise clássica e da avaliação direta da distribuição de tamanho de partículas. Para tal, foram realizados experimentos em escala de bancada. Os resultados foram avaliados à luz da abordagem clássica, dada pelo adimensional número de Camp (GT) e pela cinética de agregação e ruptura, e da distribuição de tamanhos de partículas. Verificou-se que o emprego isolado do produto GT não é adequado para representar as variações de desempenho na floculação e que o modelo clássico de agregação e ruptura pode ser influenciado pela medida indireta de turbidez, bem como pelo uso da sedimentação como etapa intermediária. Por outro lado, a avaliação direta de desempenho por meio da distribuição de tamanhos de partículas, representada pela função contínua linearizada, pode constituir ferramenta promissora na avaliação dedicada da floculação.
ABSTRACT: This article presents some considerations on the flocculation from the classical analysis and direct evaluation of the particle size distribution. For this purpose, essays in bench scale were performed. The results were evaluated in the light of classical approach, given by the dimensionless number Camp (GT) and the kinetics of aggregation and breakage, as well as particle size distribution. It has been found that the use of GT isolated product is not suitable to represent the variations in flocculation performance and the classical model of aggregation and break-up can be biased by an indirect measurement of turbidity and sedimentation as an intermediate step. On the other hand, the direct evaluation of performance by particle size distribution, represented by linear continuous function, can be a promising tool for the evaluation of flocculation.
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Objective: To explore the feasibility of using drawing ball model to predict the minimum sampling mass of powders. Methods: A drawing ball model was established by abstracting the particle of powders as small balls. Then the minimum sampling mass which representing the measured powders was calculated by the model. Microcrystalline cellulose (MCC) and starch were used as model powders and then the particle size distribution curves of them were determined at different sampling mass of 5, 10, and 100 mg. The homogeneity of samples was judged by the coincidence of the particle size distribution curves. Results: According to the drawing ball model, the minimum sampling mass of MCC was more than 5 mg and that of the starch was less than 5 mg, which were consistent with the results of verification experiment. When the sampling mass was 100 mg, it could also represent the overall MCC. Conclusion: Drawing ball model is feasible to investigate the minimum sampling mass of powders. The smaller the particle size of powders is, the less the minimum sampling mass would be.
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É consensual, no meio técnico, que unidades de desarenação devem reter partículas discretas de elevada velocidade relativa de sedimentação (por exemplo: areia, silte, cinzas, semente de frutas etc); e que desarenadores capazes de remover grãos de areia de tamanho maior ou igual a 0,2 mm removem a maior parte dos materiais que ocasionam problemas operacionais em estações de tratamento de esgoto (ETE). Entretanto, não existe concordância acerca da forma de se determinar a concentração ou a distribuição granulométrica de tais materiais no esgoto sanitário. O presente artigo apresenta um método para determinar a distribuição granulométrica da areia presente no esgoto sanitário, o qual se baseia no emprego de técnicas de análise de imagens digitais. A aplicação do método proposto demonstrou que, em média, 84 por cento da massa de areia carreada pelo esgoto sanitário afluente da ETE Jardim das Flores (Rio Claro, SP) era composta por partículas maiores ou iguais a 0,2 mm.
There is a consensus among technicians that degritters ought to remove discrete particles which present elevated settling velocities (e.g. sand, silt, ashes, fruit seeds etc.) and that units which are able to retain particles larger than or equal to 0.2 mm remove most of the material which causes operational problems to wastewater treatment plants (WWTP). Nevertheless, there is no agreement on how to determine grit concentration in wastewater and particle size distribution of this material. This paper presents a method to determine particle size distribution of grit carried by sewage based on the use of digital image analysis techniques. The use of the proposed method demonstrated that, on average, 84 percent of grit mass carried by the WWTP Jardim das Flores (Rio Claro, SP, Brazil) influent was made up of particles larger than or equal to 0.2 mm.
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O artigo apresenta um método proposto para determinação de tamanho de microbolhas de ar (DTMB) em sistemas de tratamento de água por flotação por ar dissolvido (FAD), utilizando a análise de imagem digital. Adicionalmente, é apresentado um estudo de caso com emprego de unidade em escala piloto. A aquisição das imagens foi realizada com uma câmera digital de 5.1MPixel, acoplada a conjunto de lentes. As imagens de microbolhas foram adquiridas em sistema com escoamento contínuo para eliminar as interferências causadas pela captura de amostras. O tratamento e obtenção das feições foram realizadas com o programa (freeware) "ImageTool". Os resultados apresentaram coerência com os valores reportados na literatura utilizando métodos tradicionais. O sistema mostrou-se eficaz e o método desenvolvido pode constituir ferramenta útil para estudos em outras subáreas de conhecimento.
An image analysis method proposed for assessing bubble size distribution applied to dissolved air flotation (DAF) systems for drinking water treatment is presented. Further, a pilot plant investigation is presented. A digital camera together with a group of lens was used. In order to eliminate samples interferences the images were captured in a continuous flow system working in steady state. The freeware ImageTool was applied for treating and obtaining size distribution. Results were presented in good relationship with traditional methods. The role image system showed to be efficient for image capturing and the proposed method may be an useful tool to other researches areas.