Abstract
We recently developed an in vitro testing system, namely, ESCAR (Emulator of SubCutaneous Absorption and Release). The objective of this work was to investigate drug release behaviors of unmilled and milled suspensions in ESCAR. A mass transport-based model was developed to describe the multi-step drug release process, including drug dissolution, particle settling, drug distribution/partition, and drug permeation through the membrane(s). To address the particle settling effect, a correction factor was included in the model and its value was obtained by data fitting. It was found that, for both suspensions, (i) the experimental data of various dose/formulation combinations could be fit by the developed model; (ii) the dose effect on drug release was offset by the particle settling effect. This model may help to reduce experimental efforts and facilitate subcutaneous suspension formulation development using ESCAR.
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Data Availability
The data of the IVIVC simulation is already presented in the supplementary information.
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Acknowledgements
The authors thank Mr. Ryan Grigsby for his support. The authors thank KU Nanofabrication Facility for providing the necessary resources. The authors also thank the support from NIH P30GM145499.
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H.L. contributed to conceptualization, methodology, software, formal analysis, writing—original draft, visualization, and project administration. M.J.H. contributed to writing—review and editing, project administration, supervision, and resources. All authors read and approved the final manuscript.
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Lou, H., Hageman, M.J. Development of Drug Release Model for Suspensions in ESCAR (Emulator of SubCutaneous Absorption and Release). AAPS J 25, 29 (2023). https://doi.org/10.1208/s12248-023-00799-1
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DOI: https://doi.org/10.1208/s12248-023-00799-1