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Simulating Dissolution of Intravitreal Triamcinolone Acetonide Suspensions in an Anatomically Accurate Rabbit Eye Model

PURPOSE: A computational fluid dynamics (CFD) study examined the impact of particle size on dissolution rate and residence of intravitreal suspension depots of Triamcinolone Acetonide (TAC). METHODS: A model for the rabbit eye was constructed using insights from high-resolution NMR imaging studies (...

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Autores principales: Missel, Paul J., Horner, Marc, Muralikrishnan, R.
Formato: Texto
Lenguaje:English
Publicado: Springer US 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2896643/
https://www.ncbi.nlm.nih.gov/pubmed/20467888
http://dx.doi.org/10.1007/s11095-010-0163-1
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author Missel, Paul J.
Horner, Marc
Muralikrishnan, R.
author_facet Missel, Paul J.
Horner, Marc
Muralikrishnan, R.
author_sort Missel, Paul J.
collection PubMed
description PURPOSE: A computational fluid dynamics (CFD) study examined the impact of particle size on dissolution rate and residence of intravitreal suspension depots of Triamcinolone Acetonide (TAC). METHODS: A model for the rabbit eye was constructed using insights from high-resolution NMR imaging studies (Sawada 2002). The current model was compared to other published simulations in its ability to predict clearance of various intravitreally injected materials. Suspension depots were constructed explicitly rendering individual particles in various configurations: 4 or 16 mg drug confined to a 100 μL spherical depot, or 4 mg exploded to fill the entire vitreous. Particle size was reduced systematically in each configuration. The convective diffusion/dissolution process was simulated using a multiphase model. RESULTS: Release rate became independent of particle diameter below a certain value. The size-independent limits occurred for particle diameters ranging from 77 to 428 μM depending upon the depot configuration. Residence time predicted for the spherical depots in the size-independent limit was comparable to that observed in vivo. CONCLUSIONS: Since the size-independent limit was several-fold greater than the particle size of commercially available pharmaceutical TAC suspensions, differences in particle size amongst such products are predicted to be immaterial to their duration or performance.
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spelling pubmed-28966432010-07-29 Simulating Dissolution of Intravitreal Triamcinolone Acetonide Suspensions in an Anatomically Accurate Rabbit Eye Model Missel, Paul J. Horner, Marc Muralikrishnan, R. Pharm Res Research Paper PURPOSE: A computational fluid dynamics (CFD) study examined the impact of particle size on dissolution rate and residence of intravitreal suspension depots of Triamcinolone Acetonide (TAC). METHODS: A model for the rabbit eye was constructed using insights from high-resolution NMR imaging studies (Sawada 2002). The current model was compared to other published simulations in its ability to predict clearance of various intravitreally injected materials. Suspension depots were constructed explicitly rendering individual particles in various configurations: 4 or 16 mg drug confined to a 100 μL spherical depot, or 4 mg exploded to fill the entire vitreous. Particle size was reduced systematically in each configuration. The convective diffusion/dissolution process was simulated using a multiphase model. RESULTS: Release rate became independent of particle diameter below a certain value. The size-independent limits occurred for particle diameters ranging from 77 to 428 μM depending upon the depot configuration. Residence time predicted for the spherical depots in the size-independent limit was comparable to that observed in vivo. CONCLUSIONS: Since the size-independent limit was several-fold greater than the particle size of commercially available pharmaceutical TAC suspensions, differences in particle size amongst such products are predicted to be immaterial to their duration or performance. Springer US 2010-05-14 2010 /pmc/articles/PMC2896643/ /pubmed/20467888 http://dx.doi.org/10.1007/s11095-010-0163-1 Text en © The Author(s) 2010 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Research Paper
Missel, Paul J.
Horner, Marc
Muralikrishnan, R.
Simulating Dissolution of Intravitreal Triamcinolone Acetonide Suspensions in an Anatomically Accurate Rabbit Eye Model
title Simulating Dissolution of Intravitreal Triamcinolone Acetonide Suspensions in an Anatomically Accurate Rabbit Eye Model
title_full Simulating Dissolution of Intravitreal Triamcinolone Acetonide Suspensions in an Anatomically Accurate Rabbit Eye Model
title_fullStr Simulating Dissolution of Intravitreal Triamcinolone Acetonide Suspensions in an Anatomically Accurate Rabbit Eye Model
title_full_unstemmed Simulating Dissolution of Intravitreal Triamcinolone Acetonide Suspensions in an Anatomically Accurate Rabbit Eye Model
title_short Simulating Dissolution of Intravitreal Triamcinolone Acetonide Suspensions in an Anatomically Accurate Rabbit Eye Model
title_sort simulating dissolution of intravitreal triamcinolone acetonide suspensions in an anatomically accurate rabbit eye model
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2896643/
https://www.ncbi.nlm.nih.gov/pubmed/20467888
http://dx.doi.org/10.1007/s11095-010-0163-1
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