Convective Diffusion Model for a Transport-Controlled Dissolution Rate Process

Nelson, Kyle A.; Shah, Ashok C.

doi:10.1002/jps.2600640407

Cited by 50 publications

(34 citation statements)

References 8 publications

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“…The rate of shear enters eq 3 because of the fundamental nature of the convective diffusion model. 8 The velocity profile of a Newtonian liquid flowing through the dissolution cell is parabolic as shown in Figure 2. As shown in our previous work, the rate of shear, a, at the dissolving surface is the first derivative of velocity with respect to distance (normal to the dissolving surface) evaluated at the dissolving s u r f a~e .~ This limiting derivative is shown as the stiaight line in Figure 2.…”

Section: Resultsmentioning

confidence: 99%

Mass transport in dissolution kinetics I: Convective diffusion to assess the role of fluid viscosity under forced flow conditions

Nelson¹,

Shah

1987

Journal of Pharmaceutical Sciences

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Section: Resultsmentioning

confidence: 99%

Mass transport in dissolution kinetics I: Convective diffusion to assess the role of fluid viscosity under forced flow conditions

Nelson¹,

Shah

1987

Journal of Pharmaceutical Sciences

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“…We found the example of solid dissolution into a falling film (12) was useful for correcting a misprint in the original derivation (8). In each case, the fluid velocity is constrained to one dimension, and velocity is assumed to vary linearly with distance away from the wall:…”

Section: Appendixmentioning

confidence: 99%

“…The test geometry applies a uniform shear rate across the dissolving surface whose area is held constant throughout the experiment. Although the area is not uniformly accessible to the dissolution process in the same manner as for the rotating disk, a rigorous mathematical solution can be obtained (7,8) for this problem in laminar flow. This solution has been extended by relaxing the constraint of a fixed surface concentration.…”

Section: Introductionmentioning

confidence: 99%

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Reexamination of Convective Diffusion/Drug Dissolution in a Laminar Flow Channel: Accurate Prediction of Dissolution Rate

2004

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“…The delivery of a molecule at specific time and location is a function of diffusion (molecular movement) and convection (mixing) in a dynamic system (Nelson and Shah, 1975). Fick's laws of diffusion were first adopted to provide an insight into the release and traverse of the active pharmaceutical molecules through the intestinal wall.…”

Section: Mechanism Of Drug Releasementioning

confidence: 99%

Understanding the mechanism of drug delivery from thickened fluids to aid swallowing of medications

Torres¹,

Juliana²

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Medications are often crushed and mixed with foods or fluids to aid drug delivery for those who cannot or prefer not to swallow whole tablets or capsules. Dysphagic patients have the added problem of being unable to safely swallow fluids, so thickeners are added to ensure safe swallowing. These thickened fluids are then also used to deliver crushed medications in replacement of water. This thesis explores the influence of thickened water co-administration on drug release in gastric fluid, the effect of rheological properties of these agents and their contribution to describing the mechanism of release. The literature review (Chapter 1) examines oral dosage form administration, rheological properties of these agents as a means to ensure medication delivery and mechanisms of drug release. It is highlighted that thickened fluids have the potential to alter drug release but prediction of the effect of co-administration is not currently reported.Chapter 2 investigates the delivery of medications with thickened fluids as an indicator for potential compromise of drug bioavailability. In vitro dissolution in simulated gastric fluid is investigated for crushed atenolol immediate release tablets mixed with thickened fluids. Five commercial viscosityincreasing agents of varied polysaccharide composition are used at three thickness levels prescribed for dysphagic patients (levels 150, 400, 900). All types of thickening agents are non-Newtonian shear thinning fluids. The greatest thickness (level 900) significantly restricts dissolution, and products that are primarily based on xanthan gum also significantly delay dissolution at the intermediate thickness level (level 400). The interactions of the polysaccharide chains, particularly the rigid rod type conformation of xanthan gum, traps drug molecules within it resulting in impaired dissolution. Under the conditions of this experiment, the higher concentrations of thickening agents remain in large lumps rather than disintegrating into the media. Drug release is generally affected to a greater extent by high-viscosity fluids than low-viscosity fluids at 50 s -1 , but viscosity at this single shear rate of 50 s -1 is not a good indicator for effect on drug dissolution because viscosity changes with shear rate. The determination of other rheological parameters such as viscoelasticity and the effect of breaking up of the structures may be required.To investigate whether it is possible to improve drug release from thickened fluids, in Chapter 3 the effect of the state of aggregation of the active ingredient with thickened fluids is investigated.Paracetamol is the model drug because it is available in a range of formulations with the drug in solution (elixir, dissolved effervescent tablet) or dispersion (suspension). Xanthan gum, which causes the greatest restriction on dissolution (Chapter 2), is used at level 900 as the thickener.ii Crushed tablets with thickener are prepared using manual (i.e. the standard method in clinical practice) or mechanical mixing. The unthickene...

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Convective Diffusion Model for a Transport-Controlled Dissolution Rate Process

Cited by 50 publications

References 8 publications

Mass transport in dissolution kinetics I: Convective diffusion to assess the role of fluid viscosity under forced flow conditions

Mass transport in dissolution kinetics I: Convective diffusion to assess the role of fluid viscosity under forced flow conditions

Reexamination of Convective Diffusion/Drug Dissolution in a Laminar Flow Channel: Accurate Prediction of Dissolution Rate

Understanding the mechanism of drug delivery from thickened fluids to aid swallowing of medications

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