Visualisation and quantification of subcutaneous injections of different volumes, viscosities and injection rates: An ex-vivo micro-CT study

•Ex vivo minipig subcutaneous tissues were injected with mimic drug formulations containing a contrast agent.•Micro-CT scanning provided quantifiable information on the spatial dispersion of injections at a range of volumes, rates and viscosities. Scans were taken before and after injection, allowing for the first time a direct comparison between the original and injected tissues.•Injection pressures were also recorded, providing information on tissue backpressure which allowed comparison of pressure trends with injectate dispersion patterns.•Five repeats for four injection conditions allow for the first time an assessment of the effects of injection site variability on injectate dispersion and tissue backpressure. The relevance of this variability to clinical PK studies is discussed in terms of transit distance to lymph vessels. The effects of subcutaneous (SC) injection parameters such as drug formulation volume, viscosity and injection rate on therapeutic performance and tolerability have not been established for any drug product. In this study four groups of SC injections were performed on fresh ex vivo minipig abdominal tissue samples, varying volume (0.5-1 mL), viscosity (1-11 cP) and rate (0.02-0.1 mL/s). Micro-CT provided high resolution (50 micron) imaging of the SC tissues before and after injection, enabling a detailed 3D visualisation and analysis of how both injection parameters and tissue microstructure influence spatial distribution of injectables. We found that volume was the only significant factor for spatial distribution of injectate within our design space, and there were no significant factors for tissue backpressure. Variability within test groups was typically greater than differences between group means. Accordingly, whilst the higher viscosity formulations consistently exhibited reduced spatial distribution, the sample size was not large enough to establish confidence in this result. Comparing our findings to clinical evidence, we conclude that injection site and depth are more likely to influence PK and bioavailability than volume, viscosity and rate within our experimental space.