Acetaminophen as a Model Drug to Evaluate Marketed Microcrystalline Cellulose 200 in Direct Compression
Case Study

Acetaminophen as a Model Drug to Evaluate Marketed Microcrystalline Cellulose 200 in Direct Compression

Presented at the 13th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, March 28-31, 2022, Rotterdam, Netherlands

Authors

INTRODUCTION

Microcrystalline cellulose (MCC) is a preferred filler in tablets mass production by direct compression. Within various grades, MCC 200 is one of the most suitable MCCs due to its excellent binding properties. During direct compression, it plastically deforms, maximizing the contact area of interparticle bonding creating a robust compact. Previous studies have shown that different MCC brands can affect drug product performance due to their manufacturing variables (processing conditions and particle size). The purpose of this study is to compare the MCC 200 manufactured by three companies FMC (AVICEL® PH-200), Roquette (MICROCEL® MC-200 and MICROCEL® 200 SD) and JRS Pharma (VIVAPUR® 200) and to show their performances interchangeable in the presence of acetaminophen (APAP), as a model drug.

METHODS

Materials and Formulation: Physical mixtures of 40% APAP (w/w) and 59.5% MCC 200 (w/w) from three manufacturers: FMC, Roquette and JRS Pharma were mixed in a TURBULA™ tumbling blender for 5 min. 0.5% of Mg Stearate (w/w) was then added and blended for additional 1 minute. 

Particle size distribution was measured by laser diffraction using a Master Sizer-2000 optical laser diffraction system. True density of MCCs (as powders) and in formulations were measured using a helium pycnometer AccuPyc 1330 (Micromeritics).

Flowability was determined by calculating Carr’s index based on bulk volume and tapped volume (as per USP II method using automatic tapper).

Moisture content was monitored using moisture analyzer.

Compaction: Tablets were made using 11.28 mm diameter (1 cm²) round, flat-faced TSM-D tooling with a target weight of 250 mg for all samples using a STYL’One Evolution (Medelpharm) simulating Korsch XL-400 rotary compressor. Each formulation was compressed at four peak compression forces of 5, 10, 15 and 20 kN. Three simulated compression speeds were used (1 rpm = 2100 tablets per hour (L), 35 rpm = 73500 tablets per hour (M) and 70 rpm = 147000 tablets per hour (H)).

Tablet dissolution was performed as per USP <711> requirements. API content uniformity study was performed as per UPS <905> requirements.

 

RESULTS 

Powder characterization: The particle sizes (d(0.5)) of all pure MCC 200 are around 200 µm. The moisture content for all the pure MCC 200 was around 5%. All pure MCC 200 (all brands) showed good flow properties, as well as APAP formulations with MCC 200 (all brands), are qualifying them as performant candidates for tableting by direct compression.

Compaction behavior: Tabletability of APAP formulations with MCC 200 at the same compression speed (L, M and H) ranks as follows: AVICEL® and MICROCEL® MC slightly better than MICROCEL® SD and VIVAPUR®. The lowest compression speed displays the best tabletability for all APAP formulations. All APAP formulations with MCC 200 displayed similar compressibility and compactibility profiles at the same compression speed (L, M and H; see figure 1). Ejection force is less than 200 N at all compaction speeds for all APAP formulations with all MCC 200 brands. 

 

Figure 1. Compactibility of APAP-MCC 200 (all brands) formulations simulating Korsch XL-400 rotary compressor (L = 1 rpm = 2100 tab/h, M = 35 rpm = 73500 tab/h, H = 70 rpm = 147000 tab/h)

 

Tablet Dissolution: All the APAP tablets with MCC 200 from all brands were able to release more than 80% of the APAP amount within 30 min which meets the USP requirements (see figure 2).

 

 Figure 2. APAP release profile from APAP-MCC 200 (all brands) tablet formulations 

 

API Content Uniformity Study: The acceptance values for all formulations are between 5 to 6 and less than the maximum allowed by USP (acceptance value = 15.0) (table 1).
 

Table 1. Content uniformity values of APAP-MCC 200 (all brands) formulations.

   k  s  X (%)  X (number) Condition  AV Equation  AV 
APH 200 2.4   0.23  0.94  94.15  X < 98.5 %  98.5  AV = 98.5 - X + ks  4.89
MSD 200 2.4  1.04  1.04  103.97  X > 101.5 %  101.5  AV = x - 101.5 + ks  4.96
MMC 200  2.4  0.1  0.93  92.99   X < 98.5 %  98.5  AV = 98.5 - X + ks  5.75
VVP 200   2.4 0.12   0.96  95.82   X > 101.5 %  101.5  AV = x - 101.5 + ks  5.97

 

CONCLUSION

Selecting the right excipient is critical for downstream processing. There are many brands available, and the differences between brands are mainly due to the sources of raw material and their manufacturing process. Despite these differences, our study demonstrates that MCC 200 from different manufacturers are interchangeable from compaction behavior, dissolution profile and content uniformity providing a convenient filler selection for APAP formulation.

 

REFERENCES

1. Battista, O. A., and Smith, P. A. “Microcrystalline cellulose.” Industrial & Engineering Chemistry 54, 9 (1962): 20-29. 

https://doi.org/10.1021/ie50633a003
2. Reier, G. E. and Shangraw, R. F.. “Microcrystalline cellulose in tableting.” Journal of Pharmaceutical Sciences 55, 5 (1966): 510-514.

https://doi.org/10.1002/jps.2600550513

 

AVICEL® 30 is a registered trademark of FMC, Germany.
VIVAPUR® is a registered trademark of JRS Pharma, Germany.

MICROCEL® is a registered trademark of Roquette Frères in Benelux, Brazil, Canada, Chile, France, Germany, Italy, Mexico, the United Kingdom, and the United States of America and is pending in other countries or regions. 

®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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