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A moving-boundary model of dissolution from binary drug-excipient granules incorporating microstructure.

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journal contribution
posted on 2021-04-27, 10:58 authored by Kevin M. Moroney, Lalith Kotamarthy, Indu Muthancheri, Rohit Ramachandran, Michael Vynnycky
Accurate mechanistic in vitro dissolution models can deliver insight into drug release behaviour and guide formulation development. Drug release profiles from drug-excipient granules can be impacted by variation of porosity and drug load within granules, which may arise from inherent variability in granulation processes. Here, we analyse and validate a recent model of drug release from a single spherical granule with a matrix of insoluble excipient, incorporating radial variation of porosity and drug load. The model is presented and specialised to the case where the initial drug load is large compared to the capacity of the granule's pores at solubility. In this limit, the model reduces to a single ordinary differential equation describing depletion of a shrinking, drug-saturated core. Model validation is performed using drug release data from the literature for a granule system consisting of acetaminophen and microcrystalline cellulose. A new extended model to describe dissolution from a polydisperse collection of granules is derived. The performance is compared to single particle models using equivalent spherical diameters. The developed model provides a new tool to explore the dissolution parameter space for these systems and for considering the impact of radial variation of granule porosity and drug load arising from manufacturing processes.

History

Publication

International Journal of Pharmaceutics;599, 120219

Publisher

Elsevier

Note

peer-reviewed The published OA version of this article was added to ULIR on the 07/05/2021

Other Funding information

SFI

Rights

This is the author’s version of a work that was accepted for publication in International Journal of Pharmaceutics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in International Journal of Pharmaceutics Volume 599, 15 April 2021, 120219, https://doi.org/10.1016/j.ijpharm.2021.120219

Language

English

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