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M. A. Kapin, P. J. Missel, M. Horner, R. Muralikrishnan; Complex Fluid Dynamics Simulations of Dissolution of Intravitreal Drug Suspensions in a Model Cylindrical Human Eye. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3175.
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Investigate in silico the potential influence of particle size on dissolution of Triamcinolone Acetonide suspensions in the vitreous.
Two model suspensions were placed in a cylindrical model for the human eye comprised of 4 mLs vitreous surrounded by a 0.03 cm scleral shell, including IOP-induced hydraulic flow. Suspensions were comprised of 4 mg drug divided into 18 or 486 spherical particles dispersed in a 0.1 mL cylindrical volume. A third configuration considered was a single spherical 4 mg pellet placed in the center of this 0.1 mL volume region. The convective diffusion equation was solved to provide the dynamic concentration distribution. Drug concentration was set to 20 ppm on the drug / vitreous interface. Time-dependent simulations were conducted using the VOF (Volume of Fluid) two-phase method in Fluent. Drug flux was calculated across the drug / vitreous interface, and the volume fraction in each boundary cell was adjusted at each time step to keep track of the conversion of material from the solid to the dissolved phases until all material was dissolved.
Drug release is first-order intermediate between a straight linear dependence and an exponential decay with time. The simulated dissolution of a single particle was in good agreement with the exact mathematical derivation for the Hopfenberg case of a spherical particle dissolving in a finite spherical volume, validating the simulation method. Dissolution from the two suspension models proceeded much faster than the single particle, but there was not much difference in dissolution rate between the 18 and 486 particle suspensions.
Dissolution from drug particles suspended in the vitreous proceeds primarily by diffusive rather than convective flux. Drug residence time was on the order of a few months, consistent with in vivo observations. Dissolution rate is quite insensitive to mean particle size, when the comparison is made between two suspensions confined to an identical 0.1 mL volume region.
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