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Evaluation of buprenorphine hydrochloride Pluronic® gel formulation in male C57BL/6NCrl mice

Lab Animal volume 45, pages 370–379 (2016)Cite this article

Abstract

Providing adequate analgesia while minimizing handling and stress post-surgery can be challenging. Recently, there have been commercial products made available for providing long acting analgesia in rodents. However, we find there are limitations for use in mice due to the viscosity of the product and the small dosing volumes needed. This project evaluated an in-house compounded formulation of buprenorphine easily made in the laboratory using pharmaceutical grade products. The release of buprenorphine was evaluated when compounded with two types of hydrogels (Pluronic® F-127 and F-68). Mice given buprenorphine in hydrogel (BP) demonstrated higher serum levels of buprenorphine for a longer period of time compared to mice given standard buprenorphine (Bup). However, the rate of decline in serum levels between the groups was similar; thus, it is more likely that the higher buprenorphine concentration seen in the BP group is due to the higher dose of buprenorphine given, rather than a slower release of product. Feed consumption was decreased in both groups one day after dosing; however, there was no difference in body weights. Increased activity in the open field was observed with both buprenorphine formulations, and lipemia was observed in mice given BP which persisted to at least 96 h. Based on our results, we conclude that this formulation did not sustain the release of buprenorphine or eliminate the increased activity commonly seen in mice given buprenorphine. In addition, the lipemia may confound research parameters, especially in cardiac studies and lipid metabolism studies. Therefore, we cannot recommend this formulation for use.

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Figure 1: Transition temperatures from solid to gel.
Figure 2: Data on buprenorphine release from gel solutions.
Figure 3: Comparison of locomotor activity using Optomax Activity monitor program.
Figure 4: Daily wheel revolutions.
Figure 5: Average daily feed consumption baseline (BL) was average over 3 days before dosing.
Figure 6: Average daily body weights were measured 3 days before dosing for the baseline (BL) pretreatment data.

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Acknowledgements

This research was supported by the Intramural Research Program of the National Institutes of Health and the National Institute of Environmental Health Sciences. This article may be the work product of an employee or group of employees of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), however, the statements, opinions or conclusions contained herein do not necessarily represent the statements, opinions or conclusions of NIEHS, NIH or the United States government.

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Authors and Affiliations

  1. Veterinary Medicine Section, Comparative Medicine Branch, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, North Carolina

    Terry L. Blankenship-Paris, David R. Goulding, Christopher A. McGee & Page H. Myers

  2. Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas

    John W. Dutton

  3. Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, Research Triangle Park, North Carolina

    Grace E. Kissling

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  1. Terry L. Blankenship-Paris
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Contributions

T.L.B.-P. conceived of the project. T.L.B.-P., D.R.G., P.H.M. and J.W.D. designed the experiments. T.L.B.-P., D.R.G., P.H.M. and C.A.M. conducted the experiments. D.R.G. and G.E.K. analyzed the data. T.L.B.-P., D.R.G., P.H.M., and J.W.D. prepared the manuscript. T.L.B.-P. supervised the project.

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Correspondence to Terry L. Blankenship-Paris.

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Blankenship-Paris, T., Dutton, J., Goulding, D. et al. Evaluation of buprenorphine hydrochloride Pluronic® gel formulation in male C57BL/6NCrl mice. Lab Anim 45, 370–379 (2016). https://doi.org/10.1038/laban.1106

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