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Pharmaceutical powder flowability testing plays a vital role in pharmaceutical industry. The focus on process understanding, monitoring, and control is driving manufacturers to take greater steps toward identifying possible manufacturing bottlenecks earlier in the development process. For tablet, capsule, and excipient producers, such efforts include taking a closer look at the flowability of their powders. The powder flowability affects costs, quality of production, as long as time to market and work safety. As a result, flowablity study is conducted as early as development stage, and requires as accurate as possible.
There are only two truths when it comes to powder flow analysis: Powders are a complex material and no one single test method is the best. Everything else is debatable. Thus, variety of methods with different methodology, scope, scale and standard are applied in industry. Five of them are discussed here.
In USP General Information Chapter "?1174? Powder Flow", four methods are included: angle of repose, compressibility index or Hausner ratio, flow rate through an orifice, and shear-cell methods. Though the first three have been used in industry for at least 40 years, and seem to be ï¿½ï¿½primitiveï¿½ï¿½, there are enough data to indicate that they can be correlated with manufacturing experience and are therefore of some value. Shear-cell methods is relatively new and able to provide detailed value of powder property, yet limitation lies on lack of equipment consideration and requirement of large amount of powders.
A new method using vibrating capillary addresses the problem of establishing flowability evaluation in the earlier stage in powder development, which means only extremely small amount of powder is available. Another new method is by using 1 to 2 grams powder to determine powder flow characteristics. These two methods will be discussed in detail about their development and evaluation.
Introduction of Traditional Methods
Angle of Repose
USP defines angle of repose as the "constant, three dimensional angle, relative to the horizontal base, assumed by a cone-like pile of material," which is formed when the powder is passed through a funnel-like container. The results rely heavily on the method used to form the cone. Two important variables are the height of the funnel and the diameter of the base (i.e., whether can be fixed or allowed to vary). The USP recommended procedure for conducting an angle of repose test includes having a fixed, vibration-free base with a retaining lip and maintaining a funnel height that is 2ï¿½C4 cm from the top of the powder pile as it forms.
Calculation the angle of repose (ï¿½ï¿½):
In addition to its simplicity, the angle of repose method has the advantage of having an associated general scale of flowability recommended by USP (see Table 2.1). Typically, small angle of repose represents small friction among powders and good flowability. Disadvantages include that the material may undergo segregation, consolidation, or aeration as the cone forms. The method provides a general sense of powder flowability and thus is useful as an early indication of potential fowability problems.
Table 2.1 Scale of angle of repose
Flow Character Angle of Repose
Very poor 56-65
The compressibility index and Hausner ratio as the popular powder floability testing methods are developed in recent years. They can simply and fast predict the characteristics of powder flow. Meanwhile, due to the effects of bulk density, size and shape, surface area, moisture content, and cohesiveness on the observed compressibility index, conversely, the compressibility index is considered to measure them indirectly. For the compressibility and the Hausner ratio, they can be obtained by measuring both the bulk volume and the tapped volume of a powder. These are simple methods based upon relatively quick and easy measurements and were shown to be repeatable and effective in assessing how well the powder will flow in many circumstances.
V0 is unsettled apparent volume, Vf is final tapped volume.
USP provides a generally accepted scale of flowability of the method:
Table 2.2 Scale of Flowability
Compressibility Index(%) Flow Character Hausner Ratio
<10 Excellent 1.00-1.11
11-15 Good 1.12-1.18
16-20 Fair 1.19-1.25
21-25 Passable 1.26-1.34
26-31 Poor 1.35-1.45
32-37 Very poor 1.46-1.59
>38 Unacceptable >1.6
Although compressibility tests have advantages, including easy operation, cheap equipment and general scale available, the test parameter itself, like angle of repose, is not an intrinsic property of the material. And its theoretical relation to flowability remains not clear.
Flow through an Orifice
Empirically determining the flow rate through an orifice is useful only with free-flowing materials and not cohesive materials. The flow rate is generally measured as a mass rate or a volume rate of a powder flowing from a container and, as the chapter recognizes, can be in discrete increments or continuous. Like the previous two methods, flow rate through an orifice is not an intrinsic property of the powder . Unlike for the previous two methods, however, no general scale of flowability is provided because the rate is "critically dependent" on the method. The chapter lists experimental considerations and provides general recommendations for a procedure, including general guidelines for the dimensions of a cylindrical container.
Although flow tests provide information about what the flow is, it will not tell you why the flow is what it is. If it's more cohesive or more frictional, for example, the flow tests won't tell that it's because the material is moister, or the particle size or shape changed, or something about its electrostatic charge changed. You can't determine what could have made the flow behavior change.
In an effort to put powder flow studies and hopper design on a more fundamental basis, a variety of powder shear cell tester, such as the Jenike shear tester  (fig.2.4a), in which a cell is pushed in a linear direction to get the material to shear against itself in a linear manner, and the annular ring shear tester (fig.2.4b), in which
Figure 2.4 Shear cell tester 
the material is located in an annular shear cell, have been developed. These shear testers are versatile. The parameters of yield loci representing the shear stress- shear strain relationship, internal friction angle, the unconfined yield strength, the tensile strength and some derived parameters ( such as the flow factor and other flowability indices) can be gained.
Generally speaking, a significant advantage of shear-cell methodology is a degree of experimental control. Once a test is conducted, it can help predict the bin geometry, shape, angles, surface finish, and opening sizes that one would need to prevent flow problems. A general disadvantage, however, is that the methodology is quite time-consuming. It requires significant amounts of material while a well-trained operator is necessary.
Development of two New Methods
Powder flowability based on vibrating capillary method
Recently, a method for evaluating the powder flowability has been proposed. This method is based on the analysis of powder flow in a vibrating capillary.
The experiment process is load powder into hopper ï¿½ï¿½ increase vibration amplitude (a constant rate, 0 ~130 ï¿½ï¿½m, 2min) ï¿½ï¿½ obtain the mass of particles per time ï¿½ï¿½ analyzed powder flow rate vs. vibration acceleration.
Result and Analysis
Fig. 188.8.131.52 shows all the experimental results obtained using the sample powders with different mass median diameters. Each curve indicates the average of three measurements of the mass of particles discharged from the vibrating capillary as a function of time elapsed. This figure indicates that the mass of particles increases with the mass median diameter; i.e. the flowability increases with the diameter.
Figure 184.108.40.206 Profile of mass flow rate for Dp50=13.6um
Here, the mass flow rate is expressed as a function of the vibration acceleration. The mass flow rate is zero under no vibration, but begins to increase after exceeding certain vibration acceleration. This vibration acceleration is defined as the critical vibration acceleration. There is, however, an upper limit of the mass flow rate. Both critical vibration acceleration and maximum mass flow can be used to represent flowability.
Critical vibration acceleration
The critical vibration acceleration is here determined as the value where the powder flow rate exceeds 2 mg/s. Fig. 220.127.116.11 shows the relationship between the critical vibration acceleration and the mass median diameter. Since the critical vibration acceleration is related to the static properties such as static friction and adhesiveness, the decrease in the critical acceleration implies the increase in the flowability. The flowability defined by the critical acceleration increases with the mass median diameter. In particular, for fine particles less than 20 ï¿½ï¿½m in mass median diameter, the effect of the particle diameter on the flowability is prominent, thus, slight difference of the powder flowability can be detected.
Maximum mass flow rate
The mass flow rate of particles is also related to the dynamic property, namely dynamic friction in packing structure. To characterize the dynamic flowability of each powder, we chose the maximum mass flow rate as a parameter to evaluate the complicated dynamic flowability. Fig. 18.104.22.168 shows the relationship between the maximum mass flow rate and the mass median diameter of the sample powders. It is found that the flowability defined by the maximum mass flow rate is well correlated with the mass median diameter.
Repeatability is one of the key specifications for powder flowability measurements. Fig. 22.214.171.124 shows three measurements and average value of the flowability profile of each sample powder. The profiles have different features depending on the mass median diameter of the sample powder; however, it is found that the repeatability is reasonably good.
Stability is also an important factor to evaluate the powder flow. shows the mass flow rate as a function of time elapsed. These measurements were carried out at a constant vibration acceleration (ï¿½ï¿½=324 m/s2) using powders of Dp50=12.3, 27.6, and 58.2 ï¿½ï¿½m. For smaller particles, the mass flow rate tends to fluctuate frequently (Fig. 3.2.5 (a)); however, the stability is better with increasing particle diameter (Fig. 3.2.5 (b)ï¿½C(c)). The difference in the stability is probably due to the adhesiveness of particles or the ratio of the adhesive force to the gravitational force.
Comparison with the angle of repose
shows the experimental results obtained with the two methods. For reference, the critical vibration amplitude as well as the critical vibration acceleration is given in the ordinate of the figure. From these results, it is found that there are similar features, i.e. both the critical vibration acceleration and the angle of repose decrease with the increase in mass median diameter. However, the variation of the angle of repose is very small (3ï¿½ï¿½) over 20 ï¿½ï¿½m in mass median diameter, thus, it will be difficult to evaluate slight difference. On the other hand, the variation of the critical vibration amplitude is sufficiently larger than the limit of the reliability (1ï¿½ï¿½m). Therefore, the vibrating capillary method can have a high resolution in the flowability analysis.
When review this article, in order to understanding some basic concepts, such as the preliminary testing of resonance deciding capillary vibration frequency, readers should review another related article, ï¿½ï¿½Evaluation of flowability of composite particles and powder mixtures by a vibrating capillary methodï¿½ï¿½. This method is a stable and relatively successful method on testing fine powders. And advantages are non-contact measurement method computer control 2 min measurement time, less than 5 grams powder needed and higher resolution comparing with angle of repose.
Determination of reliable powder flow Characteristics by using 1 to 2 grams powder
This method was published in 2010 as a new method to determine the powder relative flowability by using a small amount of substances . shows a schematic diagram of the experimental apparatus.
Schematic diagram of the flowability testing device
The experiment process is loading powder into the sample holder ï¿½ï¿½ holder moving vertically with the frequency of 1 HZ ï¿½ï¿½ gaining flow rate of milligrams per second.
Result and Analysis
shows the summary of all materials flowabilities testing results. The Carrï¿½ï¿½s indexes of all materials, to some extent, reflect their flowabilities. But in some particular material, such as the Avicel? PH-200, because the particle size is too large to orifice size, the Carrï¿½ï¿½s indexes data of it cannot respect to the true flow rate which should be faster than that of Avicel? PH-102. And in this article, according to the flow rate, these materials are classified into three groups as freely flowing (flow rate > 100mg/s), intermediately flowing (10mg/s <flow rate < 100mg/s) and poorly flowing (flow rate < 10mg/s).
Scanning electron micrographs
In this paper, Scanning electron micrographs are directly used to take photos of the testing materials, Figure 126.96.36.199. It records the shapes, surface texture and sizes of the powders, which may help to analyze the frictions and cohesions between particles.
Effect of using tableting lubricant
The article also briefly detects the effect of tableting lubricants when they are applied on the MCC powders (Avicel? PH-101 and PH-102). From the figure 188.8.131.52, the results show that a uniform lubricant film around the MCC particles may reduce the frictions between particles and enhance particles flowing.
The effect of humidity on MCC powders
The exploration of seasonal air humidity on MCC powder indicates that relative humidity is significant for powder flowability, figure 184.108.40.206 (a). Meanwhile, a slight change in relative humidity (figure 220.127.116.11 (b)) also can obviously affect the powder flowing rate. And the flowability decreases with the increasing of relative humidity.
Personally, the new method developed in this paper needs more experiment data and more details of device establishing to support it is a rapid flowability testing method for cohesive powders in a small scale. Such as why this device adopt 1 HZ as the frequency to measure the flowability, does any experimental data to support why the holder should be at a lower position 80% of the time and 20% of the time at upper position when the device operated. Meanwhile, in this article, it only tests the flowability of MCC powders after applying tableting lubricants, and it also only tests the seasonal air humidity fluctuation and a slight relative humidity changes on MCC powders. These experimental data are not convincing enough without testing other powders introduced in the paper.
Powder flowablility tests play a significant role in production processes and product quality in pharmaceutical industry. However, powders are a complex material and no one single test method is the best. Traditional methods such as angle of repose, flow through an orifice and compressibility index & hausner ratio, they are relatively easy to be conducted but only show part of properties that affect flowablilty. The method of shear cell, on the other hand is widely used in all kinds of powders and can gain detail data, but wasting time, requiring a great quantity powder samples and skillful operators. Capillary vibration, as a new method, can distinguish slight differences among in flowability with less than 5g of powder. Showing well repeatability, good stability and high resolution in measuring flowability of fine powders, capillary vibration method has a bright future in application. 1 to 2 grams powder determination, though as a new method published, it need provide more supplemental data and statements to convince others that this method is rapid, accurate and repeatable.