Pressurized packages provide an elegant approach to the administration of insufflations. Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland USA, 10903 New Hampshire Ave, LS Bldg 64, Silver Spring, Maryland 20993-002 USA. These data were composed of different material types, including APIs, excipients, blends and granules from nearly a decade of development projects. Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. The crucial role of granular flows in nature (landslides, debris avalanches, slope failure)1,2,3,4,5,6,7,8 and industrial processes (handling powders and granulates, compaction, additive manufacturing)9,10,11,12,13 has been at the focus cross-disciplinary research for more than thirty years14,15. The patent apparatus for measurement of pouring of powders and granules, as well as enlarged version of apparatus for measurement of angle of repose were applied for examination of granules and their mixtures. The tapped volume was measured with the Electrolab ETD-1020 Tap Density Tester (GlobePharma) after tapping in increments of 500, 750 and 1250 taps with 250 drops per minute. Fig.22. Granulations are also used as intermediates in the preparation of capsules and tablets, since they flow more smoothly and predictably than do small powder particles. Also, in an aerosol container medicated powders may be maintained in a sterile condition. Basic model granular media are composed of rigid particles with frictional contact interactions and, in contrast to interacting particles at the atomic scale or in colloids, rigid frictional particles are devoid of an intrinsic stress or time scale. J. E. 42, 127 (2019). since they flow more smoothly and predictably than do small powder particles. 143, C4016001 (2017). the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in In other words, the cohesive interactions lead to lower packing fraction (enhanced dilatancy due to cohesive forces) but the inertial effects tend to increase it. Rev. The program has in built macro to run the test and analyze the results at the end of the run. Phys. Rev. The cohesivity index went down from unlubricated granules to lubricated with 0.25% of MgSt-B or MgSt-V (Figs. The samples consisted of different grades of magnesium stearate powder including bovine, vegetable, and food grade, physical mixture powder blend consisting of a model formulation, granules prepared by various methods including slugging, high shear granulator, and fluid bed dryer. Chem. Particuology 12, 6479 (2014). This leads to a nearly constant cohesive stress as far as the material is not fully saturated54,55. ADS Google Scholar. E 85, 011301 (2012). requires a deep understanding of phenomena involved during granules formation. Moisture content, shape, surface area, and particle size along with palmitate content and other fatty acids present in the magnesium stearate might have an important role in determining the lubricity of a powder batch (16). Samples (913g) of MgSt were passed through a no. The test is made up of downward movement of probe at 20mm/s at 175 and then upward movement at 75mm/s. The second region spaced from the axis of rotation has a second angle which is also formed by its surface plane perpendicular to the axis of rotation. Douche powders are used to prepare solutions that cleanse the vagina. See more. Lubricant efficiency of MgSt-B for fluid bed granules. 3 Altmetric Metrics Abstract The objective of the present work was to carry out a systematic evaluation of flow of pharmaceutical powders and granules using compendial and non-compendial methods. geology) to characterize solids. Epub 2015 Jan 5. 161, 138147 (1993). official website and that any information you provide is encrypted 3) to provide a measure of the flow properties and compressibility of MgSt powders. As in suspensions, \(1/{c}_{t}={I}_{m}^{2}/\mu\) represents a generalized fluidity parameter of granular flows42. Phys. Rematre A., Malet, J. P., Maquaire, O., Ancey, C. & Locat, J. MathSciNet The solid lines are fitting forms similar to those used for c and c with different parameter values; see Supplementary Note2. 4). The main idea of this page is to provide relevant information in the field of the pharmaceutical industry above all. Since Im is a decreasing function of , G declines with increasing (dynamic effect) whereas c increases (quasistatic effect). All authors discussed the results and contributed to the writing of the paper. Based on CI and HR values obtained, the flow was rated as fair for physical mixture, slugged granules as well as granules prepared by high shear mixer. Than, V. D. et al. Matter 14, 259264 (2012). Fines were allowed to settle by resting the cylinders for 15min. Lindberg N. O., Palsson M., Pihl A. C., Freeman T., Zetzener H., Enstad G. Flowability measurements of pharmaceutical powder mixtures with poor flow using five different techniques. Adv. The error bars represent the standard deviation of the data over the steady-state flow. We show that, when the apparent friction and packing fraction are normalized by their cohesion-dependent quasistatic values, they are governed by a single dimensionless number that, by virtue of stress additivity, accounts for all interactions. Peer reviewer reports are available. Stauffer F, Vanhoorne V, Pilcer G, Chavez PF, Schubert MA, Vervaet C, De Beer T. Eur J Pharm Biopharm. (3) and (4). Estrada, N., Azma, E., Radjai, F. & Taboada, A. So containment should be planned for throughout the compounding procedure, and be specified in the Formulation Record. 16, 242251 (1961). Eng. Divided Powders (Chartulae; Charts; Powder Papers). When a powder flows, the average action of the resulting cohesive stress c~fcd2 is similar to a confining stress, tending to prevent from dilation during flow, to enhance the contact forces and to reduce the relaxation time under load32,38,39. They will be contaminated with powder particles. J. E 14, 341365 (2004). What are the advantages of the colorimeter? There are four characteristic stresses of different origins governing the flow: confining stress p, inertial stress i, viscous stress v, and capillary stress c. Model intermediates were also characterized for flow properties using the conventional methods. Luding, S. Collisions and contacts between two particles. Vo, T.T., Nezamabadi, S., Mutabaruka, P. et al. ALL RIGHTS RESERVED.This site is subject to the University of North Carolina Privacy Policy. The moisture content of all of the MgSt grades was about 5.4% as determined by KarlFisher titration as depicted in Table TableII (Mettler Toledo DL38, Columbus, OH). Article & Einav, I. Eddy viscosity in dense granular flows. It was found to be user independent. The rotor moves down through the powder column at 10mm/s and 5. As in dry flows27, increases and declines with increasing I but with different values and at different rates depending on the viscosity and cohesion index. The values of I and I are also very close to those obtained in the simulations of Roy et al.34 in a ring shear cell once re-expressed in terms of our definitions. 3, c and c are linear functions of : with a0.095 and b0.005. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Although our simulations were carried out under NPT conditions, we may deduce n() and t() in the NVT ensemble from (Im) and (Im). The Angle of repose and Hausner's ratio are indicative of the inter particle friction in a powder and determine the extent . Normalized apparent friction coefficient c (a) and normalized packing fraction c (b) as a function of the generalized inertial number Im defined by Eq. 1. Units of measurements are same as in Fig. In all cases, lubrication reduced the cake strength (Figs. Chem. Approximately 1015g of material equivalent to 30 in 35ml graduated cylinder was used. Schfer, J., Dippel, S. & Wolf, D. E. Force schemes in simulations of granular materials. Cohesivity of powders causes difficulties in powder flow. Cake height ratios (ratio of the initial column height) and also the cake strength (both as the mean force and also the work requiredthe area under the curve) are calculated. 20 sieve in 750g batches. Mech. In the same way, in submerged granular flows, where the viscous drag force v is present instead of cohesive stress, i may be replaced by a linear combination i+v, leading to a visco-inertial number \({I}_{v}^{2}\equiv ({\sigma }_{i}+\beta {\sigma }_{v})/{\sigma }_{p}={I}^{2}(1+\beta /St)\), where Stiv is the Stokes number. 2. The particle displacements are calculated by step-wise resolution of Newtons second law: where particle i is assumed to interact with its neighbors j via normal contact forces fn, tangential contact forces ft, capillary forces fc, and viscous forces fvis. High-shear mixer (KG5, Key International Inc, Englishtown, NJ), and fluid bed dryer (GEA Niro, Soeborg, Denmark) were used. Richard, P., Nicodemi, M., Delannay, R., Ribire, P. & Bideau, D. Slow relaxation and compaction of granular systems. This higher angle is possible between the surface of the dust pile and the horizontal plane. readily deduced from the expressions of cn and ct as a function of Im together with Eqs. Modeling granular materials: century-long research across scales. This document was uploaded by user and they confirmed that they have the permission to share Res. The angle of repose, a traditional characterization method for pharmaceutical powder flow, is also used in other branches of science (i.e. The particle size, shape, and moisture content of each of the ingredient was variable and this might contribute to a small deviations in the reading which was observed. Accessibility We see that, despite their larger variability as compared to (Im) and (Im), the data points collapse on a master curve within our statistical precision as a function of Im with the same values 0.062 and 0.075 as in (Im) and (Im). Article Through metrics such as angle of repose and added handling angles, normalized flow, pick density, apparent and derivative index; these measurements confirmed the reliability of the pulse flow in the particle size and shape distribution. After the cone from 5g of sample was built, height of the granules forming the cone (h) and the radius (r) of the base were measured. Funnel used was a stainless steel funnel and the size of the orifice was 10mm and the height from the beginning of funnel to end of orifice was 111mm. Greater is the strength, more will be a tendency to form a hard cake which is not easy to redisperse. Assessment of physical properties of granules with paracetamol and caffeine CAS of good, rapid and regular flowability) for the following reasons: 1. The blade is designed such that it can cut through the column of the powder bed reproducibly without an aid of torque systems. However, in case of granules lubricated with MgSt-V showed a different flow pattern with increasing concentrations of lubricant (Fig. We find that Zc is a decreasing linear function of (as c) and Ac is an increasing linear function of (as c); see Supplementary Fig. carried out all the simulations, analyzed the data, and prepared all the figures. The reaction equation between citric monohydrate and sodium bicarbonate is given below: Setting up a proportion to determine the amount of sodium bicarbonate that will react with 1 gm of citric acid, one has: Similar calculations show that 2.24 gm of sodium bicarbonate react with 2 gm of tartaric acid. Indeed, almost every consumer product has been in a granular state during its manufacturing process. Kinetic theory of plastic flow in soft glassy materials. Clipboard, Search History, and several other advanced features are temporarily unavailable. In case of slugged materials, addition of lubricant made the flow worse based on compendial test results as the rating went down to passable from fair. This is a simple expression that is expected to scale cohesive processes such as wet granulation and impact dynamics of cohesive aggregates. Internet Explorer). Powder flow measurements were performed on texture analyzer with powder flow analyzer attachment (TAXT.Plus, Texture technologies, Scarsdale, NY). J Pharm Sci. The key variable for inertial flows is the shear rate. The other compendial methods of powder flow characterization which includes measurements of bulk and tap density which is semi-quantitative. The simulation code is available at sourcesup.renater.fr/www/cfgd3d and upon reasonable request from the authors. This discrepancy might be due to very qualitative nature of the scale of measurements and ratings for flow properties based on these compendial methods. The measurement is made by filling a chosen weight of powder sample into a tube and a compression piston then applies a chosen consolidation force for a specified time. The sample was introduced into the sample holder by taking care not to lose any powder due to static charges or flying off. Phys. Granular materials, fine powders and nanostructured powders are widely used in pharmaceutical industrial applications [1-4]. For all the data sets F test performed to test for homogeneity of variances. (4) is obtained. Azma, E., Radjai, F. & Saussine, G. Quasistatic rheology, force transmission and fabric properties of a packing of irregular polyhedral particles. Pharmaceutical powders are formulated to exist as fine particles. Article (eds.) 8600 Rockville Pike Flow properties of powders are basically mechanical properties. https://doi.org/10.1038/s41467-020-15263-3, DOI: https://doi.org/10.1038/s41467-020-15263-3. 2 for MgSt powder. Generally, spherical and smooth surface texture granules have good flow properties whereas granules with rough texture and irregular shape have poor flow property. Lett. Lett. You are using a browser version with limited support for CSS. A granule is a large particle or grain. T.T.V. Stable Microsystems Ltd (2002). If material is not included in the articles Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Many bulk powders are used topically. Roy, S., Luding, S. & Weinhart, T. A general(ized) local rheology for wet granular materials. Please enable it to take advantage of the complete set of features! Google Scholar. This site was designed & developed by Kevin Robinson & Jason Whitley. An FT4 Powder Rheometer (Freeman Technology, Gloucestershire, U.K.) was used to measure the flow properties of granules regarding the energy required to make them flow. Hancock B. C., Vukovinsky K. E., Brolley B., Grimsey I., Hedden D., Olsofsky A., Doherty R. A. Powder Technol. The normal contact force fn is the sum of four contributions: where \({f}_{n}^{e}\) is the elastic repulsion force, and \({f}_{n}^{d}\) is the normal damping force. If F>Fcritical, the variance between two sample sets was significantly different, whereas when F