Crushing riluzole tablets: evaluation of loss of powder and active principle in a home-simulation experiment

Abstract

Objective

Swallowing difficulties cause patients with amyotrophic lateral sclerosis (ALS) to crush oral medications, falling outside the labeling instructions and entailing some risks. To date, there is no evidence about consequences of crushing riluzole tablets in a home setting. This simulation experiment evaluated the loss of powder and active principle ingredient (API) mimicking the home setting with two alternative crushing methods (A and B).

Methods

The tests were carried out by 15 volunteers without experience in the preparation of medication. Each volunteer manually crushed 5 tablets with a meat tenderizer (method A) or two spoons pressed against each other (method B). Riluzole was weighed before (W1) and after crushing (W2). Then, a subsample of crushed tablets was analyzed by HPLC to measure API content. The loss of powder was calculated as a percentage of the intact tablet weight, and the loss of API as a percentage of the labeled API content.

Results

The quantitative analysis showed a mean percentage loss of 6.27% corresponding to a mean (SD) loss of powder of 13(±13) mg. The API loss was directly related to the powder loss: overall the mean percentage of API loss was 8.53% (corresponding to a mean API loss of 4.27 ± 4.50 mg). The difference in powder and API loss was highly statistically significant.

Conclusion

Crushing riluzole tablets in a simulated home setting determined a significant loss of powder and API. These results support neurologists to evaluate formulations that minimize the need to alter the product and can improve ALS patient journey.

Keywords:

• ALS
• API loss
• crushing tablets
• powder loss
• Riluzole

Acknowledgments

The authors thank all participating volunteers for their support. The authors also thank Daniela Longo, PhD, of PopMed company, for medical writing and editorial support.

Authors’ contributions

ACa and AG contributed to the realization of the research and critical revision of the results;

ACh and IM contributed to the critical revision of the results.

All authors revised the manuscript for important intellectual concepts, read and approved the final version of the manuscript.

Declaration of interest

Data collection and analysis were carried out by Antonella Casiraghi and Andrea Gentile. Article processing charges were funded by Zambon Biotech S.A. PopMed was contracted by Zambon Biotech S.A. for medical writing and editorial support.

Adriano Chiò serves on scientific advisory boards for Mitsubishi Tanabe, Biogen, Roche, Denali Pharma, VectorX, Cytokinetics, Lilly, Zambon Biotech S.A., and Amylyx Pharmaceuticals. He has received a research grant from Biogen. He serves as a member of the independent DSMB for ABScience, AL-S Pharma AG, and Orion.

Ivan Marjanovic is a medical consultant for Zambon S.p.A and Zambon Biotech S.A.

Data availability statement

The data that support the findings of this study are available from Dr. Antonella Casiraghi from the University of Milan, Milan, Italy; restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request by e-mail to [email protected] and with permission of the Department of Pharmaceutical Sciences, University of Milan, Via G. Colombo 71, 20133 Milan, Italy.

Additional information

Funding

This study was funded by Zambon Biotech S.A. Antonella Casiraghi and received a research grant from Zambon Biotech S.A. Dr. Gentile has no conflict of interest with this work.