乳糖粉体中流动性分析检测方案(粉末流动性)

GRANUTOOLS” Lactose Powders Analysis Application Note using：GRANUFLOWTM TABLE OF CONTENTS .TABLE OF CONTENTS. ..1 NOMENCLATURE...... ..1 1. Introduction...... 1..TTheoretical Framework... 2. GranuFlow........ II. Lactose analysis...... 3 1. Material........ .3 2GranuFlow analysis ... 4II. Conclusions.... .6 Bibliography....... Appendix 1： GranuFlow theoretical background....... 9 NOMENCLATURE Letter Description Units Cb Beverloo parameter g/mm D Hole diameter mm Dmin Minimum hole diameter for powder to flow mm dpp Primary particle diameter um F Powder mass flowrate g/s RH Relative humidity % t Time T Temperature °C W Absolute humidity gH20/kgDryAir A Relative to absolute error Standard deviation (um] I. Introduction 1. TheoreticalFramework Granular materials and fine powders are widely used in industrial applications. To control and tooptimize processing methods， these materials have to be precisely characterized. Thecharacterization methods are related either to the properties of the grains [granulometry，morphology， chemical composition， ...] and to the behaviour of the bulk powder (flowability，density， blend stability， electrostatic properties， ...). However， concerning the physical behaviourof bulk powder， most of the techniques used in R&D or quality control laboratories are based onold measurement techniques. During the last decade， we have updated these techniques to meetthe present requirements of R&D laboratories and production departments. In particular， themeasurement processes have been automatized and rigorous initialization methods have beendeveloped to obtain reproducible and interpretable results. Moreover， the use of image analysistechniques improves the measurements precision. A range of measurement methods has been developed to cover all the needs of industriesprocessing powders and granular materials. However， in this application note， we will be focusedon the GranuFlow instrument. 2. GranuFlow GranuFlow is an improved laboratory silo compared to the ancient Hall Flow Meter (ASTM B213，ISO4490] and compared to the"Flow Through An Orifice"method described in the Pharmacopea(USP1174). GranuFlow is a straightforward powder flowability measurement device composed of a silo withdifferent apertures associated with a dedicated electronic balance to measure the flowrate. Thisflowrate is computed automatically from the slope of the mass temporal evolution measured withthe balance. The aperture size is modified quickly and easily with an original rotating system. Themeasurement and the result analysis are assisted by software. The flowrate is measured for a setof aperture sizes to obtain a flow curve. Finally， the whole flow curve is fitted with the well-knownBeverloo theoretical model to obtain a flowability index [Cb， related to the powder flowability)and the minimum aperture size to obtain a flow (Dmin) (for theoretical background， user can referto Appendix 1). The whole measurement is performed easily， fastly and precisely. In this paper， we used a complete set of hole diameters： 4， 6，8， 10，12，14 and 16mm. The main purpose of this application note is to provide information regarding lactose analysis forthe Pharmaceutical field. II. Lactose analysis 1.Material The powders used in this application are provided by Meggle Pharma. All these samples are madeof lactose. They are called by the manufacturer Tablettose 70， Tablettose 80， Flowlac 90 andFlowlac 100. According to supplier’s data， the physico-chemical properties of these powders aredescribed by the following table： Table 1： Lactose physico-chemical properties. Bulk density (g/l) Tapped density (g/l) Hausner ratio Tablettose 70 530 640 1.21 Tablettose 80 620 770 1.24 Flowlac 90 560 670 1.20 Flowlac 100 590 710 1.20 SEM pictures have been made in order to have an information of the particle size distribution andparticles shape： 200 pm200 pmn MAG： 100x HV： 5.0 kV WD： 9.7 mm MAG： 100x HV： 5.0 kV WD：9.7 mm Figure 1： Tablettose 70 SEM picture. Figure 2： Tablettose 80 SEM picture. MAG：100 x HV： 5.0 kV WD：9.8mm MAG： 100x HV： 5.0 kV WD：10.0mm Figure 3： Flowlac 90 SEM picture. Figure 4： Flowlac 100 SEM picture. The first observation concerns the particles shape， indeed，all Flowlac samples have sphericalshape， while Tablettose samples have irregular one. Then， with the help of ImageJ Software， the granulometric analysis of the four samples have beencarried out [dpp is the mean primary particle diameter and o the standard deviation)： Table 2： Lactose granulometric analysis. dpp (um) o (um] Tablettose 70 90.95 75.61 Tablettose 80 39.17 48.80 Flowlac 90 42.55 50.72 Flowlac 100 47.28 33.71 2. GranuFlow analysis GranuFlow analysis were performed at 26℃ and 40.0%RH (w=8.5gH20/kgDryAir]. Mass Flowratewas investigated for different hole size (from 4mm to 16mm). F is the powder flowrate (in g/s)and C the Beverloo parameter [in g/mm3). Dmin is the minimum aperture size to obtain a flow： Table 3： Raw data obtained with the GranuFlow instrument for the four lactose samples. Powder flowrate F (g/s) D (mm) Flowlac90 Beverloo Flowlac100 Beverloo Tablettose70 Beverloo Tablettose80 Beverloo 4 0.78 0.89 0.73 0.73 0.68 0.68 0.54 0.41 6 2.34 2.45 2.08 2.01 2.01 2.06 1.47 1.35 8 4.92 5.02 4.30 4.13 4.47 4.42 3.23 3.00 10 9.21 8.77 7.75 7.21 8.26 7.92 5.68 5.49 12 14.34 13.84 12.13 11.37 13.08 12.71 8.74 8.93 14 20.52 20.35 16.51 16.71 18.92 18.92 13.02 13.42 16 27.07 28.41 23.53 23.34 27.21 26.67 19.97 19.05 Cb(g/mm’) 2.80E-04 2.30E-04 2.80E-04 2.10E-04 Dmin (mm) 0 0 0.4 0.7 These results are really interesting， indeed by the look of Hausner ratio (cf. Table 1)， we can seethat the classical tap density test (“Densitap") is unable to make differentiation between onesample to another (despite the high heterogeneity in terms of samples physico-chemicalcomposition). However， GranuFlow allows to its user to make powder classification with greataccuracy (with the help of Cb and Dmin parameters). Although Flowlac 90 and Tablettose70 havethe same Cb parameter， Dmin information allows us to affirm that Flowlac90 has the best flowabilityfrom all samples and its followed by Tablettose70. Flowlac100 comes in third position， whileTablettose80 has the lower flowability. To prove these assumptions the following figure showsthe mass flowrate according to hole diameter： Lactose powders analysis -GranuFlow Figure 5： Mass flowrate versus aperture size for all lactose samples. Lines represent the Beverloo law. This graph shows the good correlation between experimental data and modeled values (withBeverloo law). This fact is highly important， because with the Beverloo model， user can make datainterpolation， and thus predicts the mass flowrate for different hole sizes. III.Conclusions √(GranuFlow allows to plot the full mass flowrate curve. GranuFlow gives information about the Beverloo law (i.e powder flowability andminimum diameter for the powder to flow in silo configuration). √GranuFlow allows to classify powders in terms of flowability， even if the classical tapdensity test is unable to see Hausner ratio difference. Bibliography Cascade of granular flows for characterizing segregation， G. Lumay， F. Boschin， R. Cloots， N.Vandewalle， Powder Technology 234， 32-36 (2013]. Combined effect of moisture and electrostatic charges on powder flow， A. Rescaglio， J.Schockmel， N. Vandewalle and G. Lumay，EPJ Web of Conferences 140， 13009 (2017). Compaction dynamics of a magnetized powder， G. Lumay， S. Dorbolo and N. Vandewalle，Physical Review E 80，041302 (2009). Compaction of anisotropic granular materials： Experiments and simulations， G. Lumay andN. Vandewalle， Physical Review E 70， 051314 (2004). Compaction Dynamics ofWet Granular Assemblies， J. E. Fiscina， G. Lumay， F. Ludewig and N.Vandewalle， Physical Review Letters 105， 048001 (2010). Effect of an electric field on an intermittent granular flow， E. Mersch， G. Lumay， F. Boschini，and N. Vandewalle， Physical Review E 81，041309 (2010). Effect of relative air humidity on the flowability of lactose powders， G. Lumay， K. Traina， F.Boschini， V. Delaval，A. Rescaglio， R. Cloots and N. Vandewalle，Journal ofDrug Delivery Science andTechnology 35， 207-212 (2016). Experimental Study of Granular Compaction Dynamics at Different Scales： Grain Mobility，Hexagonal Domains， and Packing Fraction， G. Lumay and N. Vandewalle， Physical ReviewLetters 95， 028002 (2005). Flow abilities of powders and granular materials evidenced from dynamical tap densitymeasurement， K. Traina， R. Cloots， S. Bontempi，G. Lumay，N. Vandewalle and F. Boschini， PowderTechnology，235， 842-852 (2013). Flow of magnetized grains in a rotating drum， G. Lumay and N. Vandewalle， Physical Review E82，040301(R) (2010). How tribo-electric charges modify powder flowability， A. Rescaglio， J. Schockmel， F. Francqui，N. Vandewalle， and G. Lumay， Annual Transactions of The Nordic Rheology Society 25， 17-21(2016). Influence of cohesives forces on the macroscopic properties of granular assemblies， G.Lumay， J. Fiscina， F. Ludewig and N. Vandewalle， AIP Conference Proceedings 1542， 995 (2013). Linking compaction dynamics to the flow properties of powders， G. Lumay， N. Vandewalle， C.Bodson， L. Delattre and O. Gerasimov，Applied Physics Letters 89， 093505 (2006). Linking flowability and granulometry of lactose powders， F. Boschini， V. Delaval， K. Traina， N.Vandewalle，and G. Lumay， International Journal ofPharmaceutics 494，312-320(2015). Measuring the flowing properties of powders and grains， G. Lumay， F. Boschini， K. Traina， S.Bontempi， J.-C. Remy， R. Cloots， and N. Vandewall， Powder Technology 224，19-27 (2012). Motion of carbon nanotubes in a rotating drum： The dynamic angle of repose and a bedbehavior diagram，S. L. Pirard，G.Lumay，N.Vandewalle， J-P. Pirard， Chemical Engineering Journal146，143-147(2009). Mullite coatings on ceramic substrates： Stabilisation of Al203-SiO2 suspensions for spraydrying of composite granules suitable for reactive plasma spraying， A. Schrijnemakers， S.Andre， G. Lumay， N. Vandewalle， F. Boschini， R. Cloots and B. Vertruyen， Journal ofthe EuropeanCeramic Society 29， 2169-2175(2009). Rheological behavior of β-Ti and NiTi powders produced by atomization for SLM production of open porous orthopedic implants， G. Yablokova， M. Speirs， J. VanHumbeeck， J.-P. Kruth， J. Schrooten， R. Cloots， F. Boschini， G. Lumay， J. Luyten，Powder Technology283， 199-209(2015). The influence of grain shape， friction and cohesion on granular compaction dynamics，N.Vandewalle， G. Lumay， O. Gerasimov and F. Ludewig， The European Physical Journal E (2007). Appendix 1： GranuFlow theoretical background The mass flowrate F through a circular orifice of diameter D is given by the product of the meanspeed of the grains ， the aperture area and the bulk density p. One has the generalexpression： D- The Beverloo's law is based on two hypotheses： ●1The flow is blocked when the orifice diameter is below a threshold Dmin. The grains experience a free fall before passing through the orifice，i.e. Vout =√2 g B D. Thisrelation comes from the idea that the jamming mechanism is due to the formation of a semi-spherical arch before the orifice. If this arch has a typical size proportional to the aperture，weobtain β=0，5. To be more general， the parameter β can be a free parameter. Finally， the mass flowrate expression becomes： .GranuTools APPLICATION NOTE - ALL RIGHTS RESERVEDGRANUFLOW FOR LACTOSE MEASUREMENTS 颗粒状材料和精细粉体在工业上有着广泛的应用。为了控制和优化加工方法，必须对这些材料进行精确的表征。表征方法既与颗粒的性质(粒度、形态、化学成分等)有关，也与粉体的行为(流动性、密度、共混稳定性、静电性能等)有关。然而，关于散装粉末的物理性能，大多数在研发或质量控制实验室使用的技术是基于旧的测量技术。在过去的十年中，我们更新了这些技术，以满足研发实验室和生产部门目前的要求。特别是，测量过程已经自动化，并开发了严格的初始化方法，以获得可重复和可解释的结果。利用图像分析技术提高了测量精度。