How to characterize the fluidity of pharmaceutical powders?

China Powder Network News accounts for 70% to 80% of solid pharmaceutical preparations in pharmaceutical products. The dosage forms containing solid drugs include powders, granules, capsules, tablets, powders, suspensions, etc. Crushing, classifying, mixing, granulating, drying, tableting, packaging, conveying, storage, etc. The powder properties closely related to this series of processes are particle size, bulk density, fluidity, hygroscopicity and wettability.

Physical properties of traditional Chinese medicine powder

Among them, how to accurately describe the fluidity of medicinal powder is an important basis and means to control the quality of solid preparations, especially with the popularity of powder direct pressure technology, how to design a traditional Chinese medicine powder formula suitable for direct compression, the primary The problem is to design medicinal powders with good fluidity.

Characterization of medicinal powder fluidity

The fluidity of the powder characterizes the flowability of the powder under certain specific conditions. There are three main methods for characterizing the fluidity of the medicinal powder:

• A method based on measuring the mass flow rate of a particle, including a Hall flow meter measurement, a collapse scale of a particulate matter in a low speed drum, or a mass flow rate measurement;

• Method based on measuring particle friction, including static angle of repose, shear rheology, compression measurement, etc.;

• Fractal dimension method based on particle shape, etc.

There are various methods for evaluating the fluidity of powders. The methods commonly used in the field of pharmacy are as follows:

(1) Angle of repose measurement

The angle of repose is the maximum angle formed by the free slope of the powder accumulation layer and the horizontal plane in a static equilibrium state. The angle of repose can be measured not only directly, but also by measuring the height of the powder layer and the radius of the disk, that is, tan θ = height / radius. The measurement principle is shown in Fig. 1.

Figure 1: Principle of determination of angle of repose

There are three main methods for determining the angle of repose (see Fig. 2), namely, the injection method, the discharge method, and the container tilt method.

Figure 2: Method for determining the angle of repose

(a) Injection method (b) Discharge method (c) Tilt angle method (d) Rotating cylinder method

The angle of repose is the easiest way to check the fluidity of a powder. In general, the smaller the angle of repose, the smaller the friction, and the better the fluidity of the powder. If the angle of repose of the powder is <30o, the fluidity is good; if the angle of repose of the powder is >40o (or 45o), the fluidity is poor, and measures need to be taken to ensure accurate dosage. However, in actual production, the angle of repose α < 40o can meet the production requirements of the divided dose.

Relationship between the size of the angle of repose and the fluidity of the powder

(2) Outflow velocity method

The outflow rate is described by adding the material to the funnel to determine the time required for the entire material to flow out. The measuring device is shown in Figure 3.

Figure 3: Device for measuring the fluidity of powder

The flow rate is fast and the fluidity is good; on the contrary, the fluidity is poor. This method is only applicable to powders that are free to flow. For a powder having a strong adhesion, since the powder itself cannot flow freely, measurement cannot be performed. In this case, a glass ball assist flow with a particle size of 100 μm can be added to the powder to measure the minimum amount of glass balls required for the powder to start flowing, to indicate fluidity, and the more the amount of glass balls added, the powder The worse the liquidity.

In addition, the measurement results of the outflow rate method are greatly affected by the measurement method and experimental conditions. The influencing factors mainly include the shape and material of the container, the size and shape of the pores, and the diameter and height of the powder layer in the container.

(3) Compressibility measurement method

The degree of compression is that a certain amount of powder is filled in the measuring cylinder without any vibration, and the vibrating cylinder makes the powder in the tightest state, and the difference between the final volume Vf and the initial volume V0 after the vibration accounts for the initial volume V0 is The degree of compression C can also be obtained by calculating the looseness ρ0 and the tightness ρf.

The compression formula is calculated as follows:

The Hausner ratio is closely related to rHr and the degree of compression. It is the ratio of the initial volume V0 to the final volume Vf. The formula is as follows:

The relationship between compression degree and Hausner ratio and powder fluidity

(4) Shear experiment method

The shear test method is a powder fluidity evaluated by quantitatively measuring the mechanical properties of the powder. According to the principle of shearing experiment, the method can be divided into fixed load shear test method and constant volume shear test method. In recent years, the shear test methods commonly used for the evaluation of the fluidity of medical powders are mainly as follows.

• Jenike shear test

The traditional Jenike shear test belongs to the constant pressure single-sided shear test method, and the experimental device is shown in Figure 4.

Figure 4: Schematic diagram of the Jenike shear test setup

Figure 5: Basic schematic of the Jenike experiment

• Ring shear test

The ring shear test method is different from the Jenike shear method in that the shear box exhibits a ring shape. As shown in Fig. 6, a vertical stress is applied to the upper portion of the powder, and then the lower shear box is rotated, and the annular powder layer is sheared and rotated. The shear stress can be obtained by measuring the moment.

Figure 6: Ring shear test

• Rotary shear test

The rotary shear test method (Fig. 7) exerts a force on the powder filled in the cylindrical shear box by a rotary shearing head inserted inside the powder layer. The operation is relatively simple, the human error is small, the volume of the instrument is relatively small, the amount of sample required is small, and the measurement is fast. For the pharmaceutical powder, it is most suitable to measure the fluidity by the rotary shear test method.

Figure 7: Schulze shear test device schematic

• Parallel plate shear test

Compared with the angle of repose and compression measurement methods, the parallel plate shear method based on the Jenilke shear test principle is more suitable for the evaluation of the fluidity of wet material powder.

Figure 8: Parallel plate type shear test device diagram

(5) Carr Fluidity Index Method

There are many methods for measuring the fluidity of powders. For a long period of time, the flow properties of powders are simply predicted based on the angle of repose and compressibility of the powders. However, the factors considered in these methods are relatively simple and strong. The empirical, often in the actual unit operation, the flow is very unsatisfactory, it is difficult to describe the fluidity of the powder well. Later, Carr proposed a more comprehensive method for characterizing the flow of powder by measuring 2800 powder samples, called Carr Fluidity Index.

Carr fluidity index method is the most commonly used comprehensive evaluation method in powder fluidity evaluation. By measuring the angle of repose, compression, plate angle, agglutination or uniformity of the powder, each item has a maximum of 25 points, and the measurement result is converted into points indicating the degree of high and low, and then the total is obtained by point addition. As the fluidity index FI, the powder fluidity is comprehensively evaluated.

The liquidity index FI proposed by Carr and its meaning

The method is suitable for both powders with good fluidity and powders with strong adhesion and poor fluidity, which are common in engineering applications. Its shortcoming is that only qualitative indicators are given, and its liquidity index can not be used for engineering calculations such as conveying pressure drop, mixing time, stirring power and the like.

summary

In recent years, with the development of powder technology, many new fluidity test methods have emerged. These methods attempt to quantify or comprehensively characterize powder fluidity from the perspective of statics or kinetics. Such as the drum method, multivariate analysis. However, there are many factors affecting the fluidity of the drug powder, such as particle size, particle size distribution, particle shape, bulk density, surface state, internal friction between particles, adhesion, electrostatic force, etc., so powder flowability For proper and comprehensive evaluation and characterization, it is necessary to select the appropriate rating method according to the needs. Sometimes it is not enough to rely on one measurement method or only to analyze the change of one parameter separately. It is necessary to comprehensively evaluate several fluidity measurement methods. .

Reference materials:

Li Fengsheng et al. Pharmaceutical powder technology

Wang Liang et al. Advances in research on evaluation methods of medicinal powder fluidity

Du Yan et al. Study on the Characterization Method of Chinese Medicine Powder Fluidity

Wu Fuyu.Study on Powder Flow Characteristics and Its Characterization Methods

(China Powder Network Editing / Sancha)