PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 874746

Diffusion model for drug release from suspensions I: theoretical considerations.

J W Ayres·F T Lindstrom
View original source ↗Export metadata ↓

Abstract

A new mathematical model based on physicochemical principles is presented; it does not require a "diffusion layer" for the release of a suspended drug from a semisolid vehicle. This general model has wide range application to systems where release is controlled by the diffusion rate or dissolution rate of a drug. The appropriate mathematical relationships are derived and evaluated. Theoretical drug concentration distributions in the vehicle and a membrane and the predicted cumulative drug mass uptake by blood under specified conditions are presented. The dissolution rate of solid drug in the vehicle markedly influences predicted drug release using the model presented. It is anticipated that the model will stimulate further research to confirm or reject the assumption that the dissolution rate may be slow enough to be important in the systems studied.

Explore related subjects

Biological TransportCortisoneDiffusionKineticsModels, BiologicalOintmentsPharmaceutical PreparationsSkin AbsorptionSolubilitySuspensionsJournal ArticleResearch Support, U.S. Gov't, P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

J W Ayres, F T Lindstrom. 1977. Diffusion model for drug release from suspensions I: theoretical considerations.. https://doi.org/10.1002/jps.2600660513

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Analysis of oxygen transport in a diffusion-limited model of engineered heart tissue.

Cardiac tissue engineering has made notable progress in recent years with the advent of an experimental model based on neonatal cardiomyocytes entrapped in collage gels and purified basement membrane extract, known as "engineered heart tissues" (EHTs). EHTs are a formidable display of tissue-level contractile function and cellular-level differentiation, although they suffer greatly from mass transport limitations due to the high density of metabolically active cells and the diffusion-limited nature of the hydrogel. In this report, a mathematical model was developed to predict oxygen levels inside a one-dimensional, diffusion-limited model of EHT. These predictions were then compared to values measured in corresponding experiments with a hypoxia-sensitive stain (pimonidazole). EHTs were cast between two plastic discs, which allowed for mass transfer with the culture medium to occur in only the radial direction. EHTs were cultured for up to 36 h in the presence of pimonidazole, after which time they were snap-frozen, histologically sectioned, and stained for bound pimonidazole. Quantitative image analysis was performed to measure the distance from the culture medium at which hypoxia first occurs under various conditions. As tested by variation of simple design parameters, the trends in oxygen profiles predicted by the model are in reasonable agreement with those obtained experimentally, although a number of ambiguities related to the specific model parameters led to a general overprediction of oxygen concentrations. Based on the sensitivity analysis in the present study, it is concluded that diffusion-reaction models may offer relatively precise predictions of oxygen concentrations in diffusion-limited tissue constructs.

Biological Transport↗
PubMed2007

Specific membrane recruitment of Uso1 protein, the essential endoplasmic reticulum-to-Golgi tethering factor in yeast vesicular transport.

Uso1 is a yeast essential protein that functions to tether vesicles in the ER-to-Golgi transport. Its recruitment to the ER-derived vesicles has been demonstrated in in vitro membrane transport systems using semi-intact cells. Here we report that the binding of Uso1 to specific membranes can be detected through simple sucrose density block centrifugation. The purified Uso1 protein binds to slowly sedimenting membranes generated from rapidly sedimenting P10 membranes. These membranes were produced dependent on ATP hydrolysis, contained COPII vesicle components, but had neither of the coat subunits or ER proteins, which indicates that they were representative of the uncoated ER-derived COPII vesicles. The slowly sedimenting membranes of different origins were physically linked when they were mixed in the presence of Uso1. The C-terminal acidic region was not required in membrane binding. The presence of membranes to which Uso1 could bind in the yeast cell lysate was detected using the current method.

Biological Transport↗
PubMed2007

A theoretical study of oxygen transfer including cell necrosis for the design of a bioartificial pancreas.

In an extravascular bioartificial pancreas (BAP), islet functions are probably limited by diffusive mass transfer and local consumption, leading to low oxygenation. A mathematical model based on finite elements and focusing on local oxygen transport in both the alginate core and the islets of Langerhans has been proposed to help design an efficient pancreas supply. It was possible to randomly localize islets in a hollow fiber at different densities, and the effects of hypoxia and necrosis were included in the mass transfer simulations. Thorough study of the numerical results first led to the analysis of several relevant parameters, such as necrosis factor and efficacy in terms of insulin secretion, as a way to optimize fiber geometry. The approach was then to calculate the number of islets that needed to be implanted in order to obtain a correct response in terms of insulin secretion. In most configurations, it was found to be much higher than that of ultimately functional islets, because of hypoxia and necrosis. Fiber length should thus be adjusted accordingly. Finally, we demonstrated that the compromise to be found between the reduction of the number of implanted islets and fiber length and diameter did not correspond to realistic hollow fiber systems. The alternative of using flat geometry was also envisaged with more optimistic feasibility assessments.

Biological Transport↗