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Novel application of synchrotron x-ray computed tomography for ex-vivo imaging of subcutaneously injected polymeric microsphere suspension formulations

DOI: 10.1007/s11095-020-02825-9 DOI Help

Authors: Claire Patterson (AstraZeneca) , Dean Murphy (AstraZeneca) , Sarah Irvine (Diamond Light Source) , Leigh Connor (Diamond Light Source) , Zahra Rattray (AstraZeneca)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Pharmaceutical Research , VOL 37

State: Published (Approved)
Published: May 2020
Diamond Proposal Number(s): 14632

Open Access Open Access

Abstract: Purpose: Subcutaneously or intramuscularly administered biodegradable microsphere formulations have been successfully exploited in the management of chronic conditions for over two decades, yet mechanistic understanding of the impact of formulation attributes on in vivo absorption rate from such systems is still in its infancy. Methods: Suspension formulation physicochemical attributes may impact particulate deposition in subcutaneous (s.c.) tissue. Hence, the utility of synchrotron X-ray micro-computed tomography (μCT) for assessment of spatial distribution of suspension formulation components (PLG microspheres and vehicle) was evaluated in a porcine s.c. tissue model. Optical imaging of dyed vehicle and subsequent microscopic assessment of microsphere deposition was performed in parallel to compare the two approaches. Results: Our findings demonstrate that synchrotron μCT can be applied to the assessment of microsphere and vehicle distribution in s.c. tissue, and that microspheres can also be visualised in the absence of contrast agent using this approach. The technique was deemed superior to optical imaging of macrotomy for the characterisation of microsphere deposition owing to its non-invasive nature and relatively rapid data acquisition time. Conclusions: The method outlined in this study provides a proof of concept feasibility for μCT application to determining the vehicle and suspended PLG microspheres fate following s.c. injection. A potential application for our findings is understanding the impact of injection, device and formulation variables on initial and temporal depot geometry in pre-clinical or ex-vivo models that can inform product design.

Journal Keywords: X-ray computed tomography; subcutaneous injection; microsphere; depot; imaging; vehicle

Subject Areas: Technique Development, Biology and Bio-materials

Instruments: I12-JEEP: Joint Engineering, Environmental and Processing