The effect of particle size distribution on dissolution rate and oral absorption

Hintz, Rebecca J.; Johnson, Kevin C.

doi:10.1016/0378-5173(89)90069-0

Cited by 289 publications

(183 citation statements)

References 10 publications

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“…µm for large grains (250 µm radius) under largely stagnant conditions, in agreement with Hintz and Johnson [1989]. For a stirred solution, Sugano [2008] estimated a hydrodynamic diffusion layer thickness of approximately 10 µm.…”

Section: Reactive Transport Modelingsupporting

confidence: 60%

“…This effect can be investigated using numerical modeling if the size of the diffusion boundary layer, designated as h eff above, can be estimated. Under stagnant conditions and a grain size averaging about 420 µm, the analysis of Hintz and Johnson [1989] and Sugano [2008] suggest a diffusion boundary layer of about 30 µm. If we assume that the rates determined by Tang et al [2008a] are surface reaction-controlled rates, which seems reasonable given the stirring of their solutions and the small grain size (the width of the hydrodynamic boundary layer scales with the grain size and approaches the asymptotic molecular diffusion limit for crystals less than about 10 µm), we can calculate the rates for the large crystals used in this study assuming some potential mixture of surface reaction and diffusion control.…”

Section: Interpretation Of Rates From Stirred Reactorsmentioning

confidence: 99%

“…For these calculations, a Dirichlet (fixed concentration) boundary condition is used at either 10 or 30 µm from the calcite surface. The 10 and 30 µm boundary layers were considered based on the discussions presented in Hintz and Johnson [1989] and Sugano [2008] working in the field of pharmaceutics. Hintz and Johnson [1989] presented a model for the width of the diffusion boundary layer in the case of a dispersion of grains within a stirred fluid medium.…”

Section: Reactive Transport Modelingmentioning

confidence: 99%

“…The 10 and 30 µm boundary layers were considered based on the discussions presented in Hintz and Johnson [1989] and Sugano [2008] working in the field of pharmaceutics. Hintz and Johnson [1989] presented a model for the width of the diffusion boundary layer in the case of a dispersion of grains within a stirred fluid medium. Their analysis, which was based on calibration to measured dissolution rates, determined an empirical maximum width of 30 µm for the boundary layer as grain size increased.…”

Section: Reactive Transport Modelingmentioning

confidence: 99%

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Upscaling calcium carbonate precipitation rates from pore to continuum scale

et al. 2012

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The upscaling of calcite precipitation rates in porous media from the pore (micron) to continuum (centimeter) scale is evaluated with an integrated experimental and modeling approach. Experiments using cylindrical cores packed with glass beads and calcite (Iceland spar) crystals were injected over a period of 28 days with a supersaturated mixture of CaCl 2 and NaHCO 3 to induce calcite growth. Bulk rates of precipitation based on the change in aqueous chemistry over the length of the column are compared with spatially resolved determinations of carbonate precipitation using X-ray synchrotron microtomographic imaging at the micron scale. These data are supplemented by continuously-stirred reactor experiments using the same calcite seed material so as to minimize differences in the effects of reactive site density of the seed material, and to evaluate the rate of precipitation in the absence of transport or "porous medium" effects. Calcite precipitation rates determined in the stirred flowthrough reactor in this study are considerably slower than rates determined at similar supersaturation in unseeded batch experiments by Tang et al. [2008a], although these rates are compatible with those reported in Nehrke et al. [2007] for precipitation on Iceland spar when the same normalization to reactive surface area is used. The nearly linear dependence of the rates on supersaturation cannot be attributed to a diffusion control in the case of the stirred reactors and is likely the result of multi-sourced spiral growth.Integrated precipitation rates based on column effluent chemistry from a higher supersaturation experiment are in good agreement with determinations of total carbonate precipitated based on determination of pre-and post-experiment mass in the column using X-ray microtomography. Using the rates of precipitation determined in the well-stirred flowthrough reactors, it is possible to match the spatially-resolved microtomographic and aqueous data with a coarser resolution continuum model using volume-averaged flow and reactive surface area if the generation of new reactive surface area is accounted for. A nucleation or surface roughening event, which is most pronounced within two millimeters of the column inlet where the supersaturation is highest, is recorded by both BET analysis, which indicates an increase in specific surface area from 0.012 m 2 •g -1 to a value of 0.21 m 2 •g -1 for neoformed calcium carbonate, and by X-ray microtomography. The best fit of the column X-ray microtomography data is provided by simulating calcite precipitation either as a single nearly linear rate for multi-sourced spiral growth, or as two parallel rates that include the spiral growth model and a 2D heterogeneous nucleation model modified by a partial diffusion control, although nucleation needs to be relatively minor on a mass basis in order to match the data. The combined experiments and modeling indicate that it is possible to develop upscaled quantitative models for porous media reactivity, but changes in such propert...

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Section: Reactive Transport Modelingsupporting

confidence: 60%

Section: Interpretation Of Rates From Stirred Reactorsmentioning

confidence: 99%

Section: Reactive Transport Modelingmentioning

confidence: 99%

Section: Reactive Transport Modelingmentioning

confidence: 99%

See 2 more Smart Citations

Upscaling calcium carbonate precipitation rates from pore to continuum scale

et al. 2012

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“…In their research on the effect of particle size on distribution and oral absorption, Hintz et al [7] established a model, for theoretically simulating the absorption, by using their dissolution and permeation parameters. The Noyes-Whitney type equation was used to describe the dissolution model.…”

Section: B Related Workmentioning

confidence: 99%

Molecular Dynamics Study of Oral Medicine Delivery Rates Attributed by Two Drug Particles’ Shapes

Soong¹,

Lin²

2013

IJBBB

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Abstract-This paper presents an investigation of oral medicine delivery from a non-traditional point of view, namely, delving into the rates of delivery attributed by two different drug particle's shapes in cylindrical and spherical models. The methodology employed is molecular dynamics (MD). The approach leads to the development of an MD computer simulation program for the establishment of generic parametric databases for follow on scientific comparisons on the solubility rates of particle models in various shapes of interests. Einstein's fluctuation-dissipation equation is referred to in the calculation of diffusion coefficients of given particle models within the MD simulation. This also facilitates the study on the impact on solubility and diffusion of oral medicine particles due to the rates of change of radius and of mass with different weights and sizes. In addition, the dependency of solubility on a cylindrical drug particle's aspect ratio as well as the control on the kinetics of drug release based on diffusion speeds are evaluated. The study concludes on a comparison of the solubility of a sphere versus that of a cylinder with the same mass. The results demonstrate that with the same given mass, the solubility of a spherical particle is less than that of the cylindrical shape. It is also revealed that an increase in the diffusion coefficient for a particle with fixed mass will in turn raise its solubility. However, the solubility and the diffusion coefficient of a particle with fixed radius are inversely proportional.

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Particle Size of Drug Substance and Product Content Uniformity—Theoretical Considerations

Johnson

2008

Formulation and Analytical Development for Low‐Dose Oral Drug Products

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The effect of particle size distribution on dissolution rate and oral absorption

Cited by 289 publications

References 10 publications

Upscaling calcium carbonate precipitation rates from pore to continuum scale

Upscaling calcium carbonate precipitation rates from pore to continuum scale

Molecular Dynamics Study of Oral Medicine Delivery Rates Attributed by Two Drug Particles’ Shapes

Particle Size of Drug Substance and Product Content Uniformity—Theoretical Considerations

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