Method for Evaluating the Flowability of Pharmaceutical Tablet Powder
2019-11-25Application Note
This note evaluates powder flowability and filling ability for pharmaceutical tableting using angle of repose, compression ratio, and Hausner ratio, as these properties critically impact manufacturing and drug quality.
| Product | PowderPro A1 |
| Industry | Pharmaceuticals |
| Sample | Pharmaceutical Tablet Powder |
| Measurement Type | Powder Characteristics |
| Measurement Technology |
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Abstract: Tableting of powders is a conventional pharmaceutical manufacturing technology of solid preparation. The properties of the powders, such as flowability, filling ability and compressibility, not only affect the mixing and transfer of the powders in tableting process, but also affect the quality indicators for medication preparation such as the weight variation and the uniformity of the content. Under the circumstances that some of the pharmaceutical powders are of poor flowability or poor compressibility, it is recommended to choose excipients with good flowability, filling and compressibility to improve the powder properties[1] besides improving equipment performance. In this paper, the flowability and filling ability of the powders will be evaluated by parameters such as angle of repose, compression ratio, Hausner ratio and Kawakita equations to powder compaction.
Relationship between Angle of Repose and Flowability
The angle of repose is the internal angle between the surface of the powder pile and the horizontal surface when the powders are in static equilibrium. When the powders are poured onto a horizontal surface, a conical pile and thus angle of repose will form. Angle of repose can reflect the coefficient of friction between the powder particles. The larger the angle of repose is, the larger the coefficient of friction is and the worse the flowability of the powder will be. Generally speaking, the flowability of the powder can satisfy the requirements for tableting process when the angle of repose is less than 40°. If the value of angle of repose is higher than 40°, it is suggested to improve the flowability of the material by modifying the particle surface or adding excipients.
Relationship between Compression Ratio and Flowability
The difference between the tapped density and the bulk density divided by the tapped density equals to the compression ratio. Compression ratio is easy to calculate and through this parameter, the flowability of active ingredients, excipients, and prescription drugs can be compared efficiently. The smaller the degree of compression, the better the flowability of the powder. The relationship between compression ratio and flowabiliy is shown in the following table [3]. When the compression ratio is from 5% to 10%, the powder flowability is excellent. If the powder flowability is from 11% to 15%, the powder flowability is good. And when the ratio is from 16% to 20%, the powder flowability is just average. It is poor when the compression ratio is from 21% to 35%. [2].
| Flowability | Compression Ratio | Hausner Ratio |
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Excellent
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＜10%
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1.00 ~ 1.11
|
|
Good
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11%~15%
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1.12 ~ 1.18
|
|
Average
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16%~20%
|
1.19 ~ 1.25
|
|
Eligible
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21%~25%
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1.26 ~ 1.34
|
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Poor
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26%~ 31%
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1.35 ~ 1.45
|
|
Terrible
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32%~ 37%
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1.46 ~ 1.59
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Can hardly flow
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>38%
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>1.6
|
Relationship between Hausner Ratio and Flowability
The Hausner ratio is the ratio between the tapped density and the bulk density of the powders. When the Hausner ratio is greater than 1.35, the powder is viscous with poor flowability and filling ability. When the ratio is less than 1.2, it means the powder has good flowability and filling ability. The relationship between Hausner ratio and flowabiliy is shown in the following table [3].
Kawakita Equations Analyzing Flowability and Filling Ability of the Powders
The Kawakita equations are used to describe the relationship between the pressure and the volume of the compressed materials. It was proposed by Kimio Kawakita in 1956 as an empirical formula, and then theoretically derived. In 1963, the following theoretical equation was proposed:
C=abp/(1+bp) (1)
In the equation above, p represents the force per unit area; a is the bulk porosity; c is the volume compression ratio and b represents the compressibility factor. In this paper, the pressure is changed to the number of vibrations, and the constant in the equation can reflect the flowability and filling ability of the powders.
The equation can be transformed into the formula as below.
n/C=n/a+1/ab (2)
In equation (2), n is the number of taps; C is the reduction percentage of the relative volume of the powders and a, b are constants. If the number of taps n is infinite, a and b can be expressed by equations (3) and (4).
a=C∞=（V0-V∞）/ V0 (3)
1/b=n（Vn-V∞）/ (V0-Vn) (4)
According to the postulate, a represents the final volume reduction. The smaller the value of a is, the better the flowability of the powders will be. The smaller the 1/b is, the smaller the number of taps required to reach the minimum volume that can be filled will be, indicating better filling ability of the powders.[4]
Comprehensive Carr Index for Evaluating Flowability
According to the United States Pharmacopoeia and the European Pharmacopoeia, the method of measuring inter-particle friction is generally used. This means the measurement results of indicators including the angle of repose, compression ratio, angle of spatula, agglutination and uniformity of the powder will be indexed based on their influence on the flowability. Then the indexes will be summed to evaluate the flowability of the powders. According to Carr's flow index method, the powders with Flow Index(FI) no less than 60 is the powders with good flowability, which is convenient for transfer; when the FI is from 40-60, the powders are prone to block the transfer pipe; when the FI is less than 40, the powders are of poor flowability, which means inconvenience in transfer. Besides, powders with FI lower than 60 are supposed to be activated in manufacturing process.
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Flow Index (FI)
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Flowability Performance
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90 ~ 99
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Excellent flowability, no conical pile forms and no need for aid.
|
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80 ~ 89
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Good flowability, normally no conical pile forms and no need for aid.
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70 ~ 79
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Medium flowability, no need for aid, may need vibration.
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60 ~ 69
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Average flowability, powder bridging may occur at the marginal place.
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40 ~ 59
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Poor flowability, needs vibration or agitation.
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20 ~ 39
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Terrible flowability, needs powerful vibration or agitation.
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0~ 19
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Very very poor flowability, special measures are required.
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There are many measuring apparatus for characterizing powder flow parameters mentioned above. However, due to the low degree of standardization, usually the measurement results are greatly affected by man-made causes: when the same powders are measured by different instruments, the data obtained are often different, which affects the objectivity of the measurement results and thus affects the manufacturing process, product quality and productivity. The intelligent all-around powder characteristics tester produced by the Bettersize Instruments meets the requirements of various international standards and pharmacopoeia, and can satisfy the needs for flowability measurement with precise results hardly influenced by man-made causes.
References
[1] Gao Chunsheng. Direct powder tableting process: a booster for the overall development of the pharmaceutical industry [J]. International Journal of Pharmaceutical Research, 2009, 36(1): 1-5.
[2] Cui Fude. Pharmacy [M]. 6 edition, Beijing: People's Medical Publishing House, 2007: 330-333.
[3] Wang Chenguang, Fang Jianguo. Measurement and application of drug powder flowability[J]. Chinese Journal of New Drugs, 2013, 22(7): 809-813.
[4] Chen Shengjun, Zhu Jiabi et al. Evaluation of powder properties of commonly used excipients for direct tableting of powders [J]. Chinese Journal of Pharmaceutical Industry, 2013, 44(7): 1010-1013.
About the Authors
| Qingyu Guan Application Engineer @ Bettersize Instruments |
BeDensi T Pro SeriesIt can measure the bulk density and tapped density with 1.0% repeatability.
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