Textured Mannitol Tabletability using a Rotary Tablet Press Simulator

Situation

Mannitol manufacturing

• Synthetically produced, hydrogenation or fermentation (1, 2).
• Naturally present in certain plants, extraction from algae.

Mannitol uses

• Mainly as diluent in tablets, capsule or freeze-dried formulations, or as a drug carrier in dry powder inhalers. 3, 4
• Low moisture content and non-hygroscopic character, use with active ingredients that are sensitive to moisture.

STYLCAM 200 R press simulator

• Simulate the compression profiles of various rotary tablet presses.
• Strain gauges and potentiometric displacement transducers on the upper and lower punch.
• Variation of the velocities of compaction.
• Including precompression before the main compression.

Challenge

Investigation and performance of the compaction behavior of different textured mannitols with a rotary press simulator.

Solution

Textured mannitol DC products

• PEARLITOL® 200 SD (Roquette) / Batch 1 and 2
• Competitor A (Provider A) / Batch 1 and 2
• Competitor B (Provider B)
• Magnesium Stearate VEG (Baerlocher)

Particles and tablets characterization

Compression

• PEARLITOL® 200 SD mannitol punches: 11.28 mm flat and 10R9 mm convex/ 1.2% of lubricant
• Competitor A punches: 11.28 mm flat and 10R9 mm convex/ 1.2% of lubricant
• Competitor B punches: 10R9 mm convex/ 1.2% of lubricant

Results

Characterization and tabletability

PEARLITOL® and Competitor A

Graph 1. Particle size distribution

Figure 1. SEM picture of PEARLITOL® (a) and Competitor A (b)

Graph 1
PEARLITOL® 200 SD showed homogeneous particle size distribution with approximately same results for batches 1 and 2.
Competitor A had different PSDs and more heterogeneous particle size.
Figure 1 shows SEM pictures of textured mannitol with spherical particles for PEARLITOL® (a) and Competitor A (b).
For Competitor A, particle size was more heterogeneous with large and small particles which corroborated with the PSD results.

Graph 2. Tabletability graph with flat punches – Competitor A

Graph 2
It shows tabletability performance with flat punches at 30 tabs/min and 1.2% of lubricant.
Competitor A had slightly higher tablet hardness than tablets made from PEARLITOL® 200 SD.
Graph also shows high standard deviation value at 30 kN of compression force. For both mannitols, no hardness variation was observed for batch 1 and batch 2.

Graph 3. Tabletability graph with convex punches – Competitor A

Graph 4. Tablet mass variation

Graph 3
It shows tabletability results with convex punches ø10R9 at a compression speed of 10 tabs/min and a lubricant concentration of 1.2%.
Competitor A had higher tablet hardness than PEARLITOL®. However, standard deviation of the hardness values were lower for PEARLITOL® than Competitor A.
High standard deviation on hardness value could be due to capping or poor powder die filling. In that case, the results suggest that PEARLITOL® had better powder die filling and more regular tablet mass than Competitor A.
This difference in performance was due to the homogeneous particle size distribution of PEARLITOL®, providing a good powder flow and die filling during compression. Standard deviation value on the tablet mass was also higher for Competitor A than PEARLITOL®.

PEARLITOL® and Competitor 

Graph 5. Tabletability graph with flat punches – Competitor B

Graph 5
It shows tabletability performance with convex punches D10R9 at a compression speed of 10/25/40 tabs/min and a lubricant concentration of 1.2%. Competitor B had lower tablet hardness than PEARLITOL®. Even at high compression speed, it was still possible to get tablet hardness values close to 200 N.

Graph 6. Ejection force with flat punches – Competitor B

Graph 6
It shows the tablet ejection forces for PEARLITOL® and Competitor B. Ejection forces were similar for the same concentration of lubricant (1.2%) for the mannitol DC.

Conclusion

The rotary press simulator STYLCAM 200R was used for characterizing the following properties of PEARLITOL® 200SD in comparison with competitor textured mannitol: the batch-to-batch variation, the tabletability performance and the behavior of the powder during compaction. The rotary tablet press simulator STYLCAM is a powerful piece of equipment to quickly study powder performance on tableting with a small amount of product and short trial time.

References

1. Devos, Francis (1995). Brevet américain n°5, 466,795. FRANCE: U.S. Patent and Trademark Office.
2. Soetaert, W., D. Schwender, K. Buchholz, and E.J. Vandamme. “A wide range of carbohydrate modifications by a single organism: Leuconostoc mesenteroides.” Prog. Biotechnol, no. 10 (1995): 351-358.
3. Bolhuis, G.K., Erik G. Rexwinkel, and Klaas Zuurman. “Polyols as Filler-binders for Disintegrating Tablets Prepared by Direct Compaction.” Drug Development and Industrial Pharmacy 35, no. 6 (June 2009).
4. Kaialy, Waseem, Mohammed N. Momin, Martyn D. Ticehurst, John Murphy, and Ali Nokhodchi. “Engineered Mannitol as an Alternative Carrier to Enhance Deep Lung Penetration of Salbutamol Sulphate from Dry Powder Inhaler.” Colloids and Surfaces B: Biointerfaces 79, no. 2 (September 2010): 345-56.

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