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Feasibility of Focused Beam Reflectance Measurement (FBRM) for Analysis of Pharmaceutical Suspensions in Preclinical Development

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Abstract

This study examined the use of focused beam reflectance measurement (FBRM) for qualitative and quantitative analysis of pharmaceutical suspensions with particular application to toxicology supply preparations for use in preclinical studies. Aqueous suspensions of ibuprofen were used as prototype formulations. Initial experiments were conducted to examine the effects of operational conditions including FBRM probe angle, probe location, and mixing (method and rate of mixing) on the FBRM analysis. Once experimental conditions were optimized, the homogeneity and sedimentation-redispersion of particles in the suspensions were assessed. Ibuprofen suspension under continuous agitation was monitored using FBRM for 60 h to study particle size change over time. Another study was performed to determine if particle count rates obtained by FBRM could be correlated to suspension concentration. The location and the angle of the FBRM probe relative to the beaker contents, and the rate and the method of mixing the suspension were found to be sensitive parameters during FBRM analysis. FBRM was able to monitor the process of particle sedimentation in the suspension. The attrition of ibuprofen particles was detectable by FBRM during prolonged stirring with an increase in the number of smaller particles and decrease in the number of larger particles. A strong correlation was observed between particle count rate by FBRM and ibuprofen concentration in the suspension. Also, change in content uniformity in the suspension at different locations of the beaker was represented by FBRM particle count. Overall, FBRM has potential to be a useful tool for qualitative and quantitative analysis of pharmaceutical suspensions.

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Acknowledgements

The authors thank Kevin Shepard of Boehringer Ingelheim for collaboration on the design of the FBRM probe. Also, the authors thank BASF Chemicals for providing the ibuprofen. The authors thank Boehringer Ingelheim Pharmaceuticals, Inc., for supporting this work as a part of Kaushalkumar Dave’s summer internship. The authors thank Anjan Pandey of Mettler Toledo for helpful suggestions for this manuscript.

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Author notes

  1. Kaushalkumar Dave

    Present address: Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 20993, USA

Authors and Affiliations

  1. Material and Analytical Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, 06877, USA

    Kaushalkumar Dave, Paul E. Luner, Cecile Forness, Doris Baker, Corinne Jankovsky & Shirlynn Chen

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  1. Kaushalkumar Dave
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  2. Paul E. Luner
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  3. Cecile Forness
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  4. Doris Baker
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Correspondence to Kaushalkumar Dave or Paul E. Luner.

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Dr. Kaushalkumar Dave is currently employed at the United States Food and Drug Administration (FDA). This article reflects the views of the authors and should not be construed to represent FDA’s views or policies.

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Dave, K., Luner, P.E., Forness, C. et al. Feasibility of Focused Beam Reflectance Measurement (FBRM) for Analysis of Pharmaceutical Suspensions in Preclinical Development. AAPS PharmSciTech 19, 155–165 (2018). https://doi.org/10.1208/s12249-017-0819-9

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  • DOI: https://doi.org/10.1208/s12249-017-0819-9

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