How to Measure the Powder Friability
Case Study

How to Measure the Powder Friability

Presented at the 4th European Conference on Pharmaceutics, 20-21 March 2023, Marseille - France

Authors

INTRODUCTION

Excipients and drug substances are exposed to major mechanical stress during the pharmaceutical processing. Common manufacturing steps, such as dry blending, transportation or filling could cause the formation of dust. This is an issue in the pharmaceutical industry by harming production steps but also with its exposure of the workforce. 

Understanding the fate of powders under stress helps to select the most appropriate excipients for a dedicated application. The European Pharmacopeia does not propose any test method to measure the powder friability, but it gives with Ph. Eur. 2.9.41 a method related to the friability of granules. This test uses specific equipment (Friabimat SA-400). This study explores its usefulness for the characterization of the excipient friability.

Alternative analytical routines were screened for comparison. The idea is to propose a discriminative method, better adapted for the differentiation of excipients.

 

OBJECTIVES

This work tries to establish a universal method to understand and to quantify the powder friability. Two different methods were tested; its correlation was checked by using common excipients for direct compression (DC) or capsule filling.

 

MATERIALS AND METHODS

Materials

Common DC binders from the polyols family were selected, considering different production technologies to obtain it.

Mannitol:

PEARLITOL® 200 SD (Roquette Frères, Lestrem, France) – spray dried
PEARLITOL® 400 DC (Roquette Frères, Lestrem, France) – granulated
PEARLITOL® 200 GT (Roquette Frères, Lestrem, France) – granulated

Sorbitol:

NEOSORB® P 300 C (Roquette Frères, Lestrem, France) – crystallized
NEOSORB® P 550 SD (Roquette Frères, Lestrem, France) – granulated

Methods

Two different analytical methods were developed and compared.

Powder friability, using a three-dimensional blender

Pre-tests helped to select the most appropriate powder stress conditions, permitting the discriminative testing without facing an artificially excessive powder destruction. The evolution of the fine fraction was monitored by Laser measurement (Master Sizer 3000).

 

Figure 1. Evolution of the particle size distribution under mechanical stress, as PEARLITOL® 200 SD mannitol powder. (200 glass beads–Mixing times 5 min, 10 min 20 min and 30 min)


The following test routine was retained:

  • Weigh precisely 10 g of the prepared powder without sieving.
  • Put it in an adapted glass container, together with 200 or 400 glass beads of 4 mm.
  • Mix in a three-dimensional blender such as Turbula with a speed of 49 rpm for 5 min.
  • Measure the particle size distribution of the sample with a Mastersizer MS-3000, with Aero S Dry Powder accessory (with three replicates per sample, without air pressure).

The evolution of sieve fraction under 100 µm gives the friability result in % => fractionafter test – fractioninitial.

 

 

Figure 2. Turbula mixer, used for method 1

  

Powder friability, using a Friabimat SA-400

The following test was adapted from EP 2.9.41 “Friability of Granules and Spheroids”:

  • Weigh precisely 10 g of the powder without prior sieving.
  • Put it in an adapted glass container.
  • Shake for 240 s at the highest frequency, 400 oscillations/min.
  • Measure the particle size distribution of this powder with a Mastersizer MS-3000 before and after shaking, using an Aero S Dry Powder accessory (with three replicates per sample, without air pressure).

The evolution of sieve fraction under 100 µm gives the friability result in % => fractionafter test – fractioninitial.

 
 

Figure 3. Friabimat SA-400 used for method 2

 

RESULTS

With both alternative methods, the evolution of the sieve fraction below 100 µm was measured.

 

Table 1. Obtained powder friability data according to the methods used.

 Material  Powder Friability (%)
 Method 1  Method 2
 200 glass beads 400 glass beads  -
PEARLITOL® 200 SD  3.33  11.42  3.23
PEARLITOL® 200 GT  1.79  3.48  0.46
PEARLITOL® 400 DC  2.45  2.8  0
NEOSORB® P 550 SD  0.81  3.19  0.01
NEOSORB® P 300 C  0  0  0

 

Table 1 summarizes the results with some selected polyols, applying both analytical methods. If we consider only method 1 with different number of glass beads and with equivalent mixing time, we observe different stress sensitivities. Indeed, the number of glass beads are of significant importance for the powder friability of many products, such as Pearlitol® 200 SD mannitol, Pearlitol® 200 GT mannitol and Neosorb® P 550 SD sorbitol. On the other hand, no impact or evolution observed for the friability results with Neosorb® P 300 DC sorbitol and Pearlitol® 400 DC mannitol. Anyhow, both products are found to have a very low friability itself.

When comparing both methods, method 2 seems to give lower friability results compared to method 1. The use of glass beads tends to add additional stress to the powders during the test. This type of stress is not applied with method 2. Only Neosorb® P 300 C gives equivalent results, whatever methods used.

Both for sorbitol and for mannitol, a correlation between the powder friability and powder production process was observed. Spray-dried products have higher friability than granulated ones.
We consider that method 1 is the more discriminative method to challenge and compare different products. It could help to select the most appropriate excipients for an industrial process.
Method 2 is much more representative of the industrial production process. Its results are closer to manufacturing reality.

 

CONCLUSION

The characterization of the powder friability is possible. Method 2, adapted to from EP 2.9.41 (Friability of Granules and Spheroids), seems to be more adapted to test the powder friability as observed in the pharmaceutical industry.

 

REFERENCES

European Pharmacopoeia 2.9.41 Friability of granules and spheroids

 

® Registered trademark(s) of Roquette Frères. The information contained in this document is to the best of our knowledge true and accurate, but all instructions, recommendations or suggestions are made without any guarantee. Since the conditions of use are beyond our control, we disclaim any liability for loss and/or damage suffered from use of these data or suggestions. Furthermore, no liability is accepted if use of any product in accordance with these data or suggestions infringes any patent. No part of this document may be reproduced by any process without our prior written permission. For questions about a product’s compliance with additional countries’ standards not listed above, please contact your local Roquette representative. 

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