PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 2715937

Accessibility factors for diffusion-controlled drug delivery systems.

R S Harland·N A Peppas
View original source ↗Export metadata ↓

Abstract

The idea of accessibility factors or parameters is introduced to describe the ability of a planar or spherical controlled-release system to deliver a specific drug (with a known diffusion coefficient) within a desired period of time. The accessibility factors are the maximum and minimum values of the drug diffusion coefficient, the geometric dimensions of the system, and the release time. The solutions of the general diffusion equations are plotted as generalized diffusional diagrams, indicating the accessibility region for drug delivery. Deviations from the quasi-equilibrium conditions can be represented in these diagrams.

Explore related subjects

Delayed-Action PreparationsDiffusionModels, BiologicalJournal ArticleResearch Support, U.S. Gov't, Non-P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

R S Harland, N A Peppas. 1989. Accessibility factors for diffusion-controlled drug delivery systems.. https://doi.org/10.1002/jps.2600780215

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

KEEP EXPLORING

Related citations

PubMed2006

Haloperidol-loaded PLGA nanoparticles: systematic study of particle size and drug content.

We have produced haloperidol-loaded PLGA/PLA nanoparticles by using two emulsification-solvent evaporation methods: homogenization and sonication. We have established how five independent processing parameters and two materials characteristics control the particle size and drug content. The interdependencies between processing and materials parameters and the subsequent nanoparticle characteristics are discussed in terms of underlying scientific principles that are broadly applicable to the production of drug-loaded polymer nanoparticles. This level of understanding should quicken the pace of designing protocols for making new drug-PLGA nanoparticles. It was determined that the particle size of haloperidol-loaded PLGA/PLA nanoparticles is effectively controlled by the amount of shear stress transferred from the energy source to the organic phase, which is strongly correlated to the following parameters: type of applied energy, aqueous phase volume, and polymer concentration in the organic solvent. The drug content of these nanoparticles is controlled by reducing the diffusion of the drug from the organic to the aqueous phase during the solvent evaporation stage of the preparation and by increasing the drug-polymer interactions. The following significantly inhibit drug diffusion: large particle size, higher polymer concentration and polymer molecular weight, and reducing the drug solubility in the aqueous phase by adjusting the pH. Specific drug-polymer interactions are engineered by optimizing the lactide to glycolide ratio (L:G ratio) and including specific polymer end groups. When optimized, the drug-loaded PLGA/PLA nanoparticles contain as much as 2.5% haloperidol.

Delayed-Action Preparations↗
PubMed2006

Silk microspheres for encapsulation and controlled release.

A method was developed to prepare silk fibroin microspheres using lipid vesicles as templates to efficiently load protein drugs in active form for controlled release. The lipid was subsequently removed by methanol or sodium chloride treatments, resulting in silk microspheres consisting of beta-sheet structure and about 2 mum in diameter. NaCl treated microspheres had smoother surfaces compared to the methanol treatments based on SEM analysis, and both types of microspheres had a mixture of multilamellar and unilamellar structures. A model protein drug, horseradish peroxidase, was encapsulated in the microspheres. Freeze-thaw cycles during preparation led to higher loading of the peroxidase due to improved mixing between the silk and drug, while without this process the drug and silk remained in separate layers or domains in microspheres. This partitioning was determined with fluorescein-labeled silk and rhodamine-labeled dextran. Small molecules such as the enzyme substrate 3,3',5,5'-tetramethylbenzidine, Mw=240 Da, and its oxidized product freely diffused through the MeOH- and NaCl-processed silk microspheres so that enzyme loading and activity could be determined. Enzyme activity was retained during processing and in the final microspheres. The enzyme release profile depended on the NaCl-process used in microsphere preparation. The physically cross-linked beta-sheet structure of silk fibroin and the residual lipids in the microspheres played important roles in controlling enzyme release profiles. The silk microspheres have the potential for diverse applications where controlled protein release from biocompatible, mechanically tough, and slowly biodegradable carriers is desirable.

Delayed-Action Preparations↗
PubMed2006

Dissolution profiles of nonprescription extended-release niacin and inositol niacinate products.

PURPOSE: The dissolution profiles of nonprescription extended-release niacin and inositol niacinate products were studied using the prescription extended-release niacin, Niaspan, as a reference. METHODS: Seven nonprescription extended-release and 12 nonprescription inositol niacinate products were collected from community and online pharmacies in the United States. Extended-release Niaspan was used as a reference. Dissolution profiles were examined by the United States Pharmacopoeia dissolution test, using a paddle method. Release samples were removed every 30 minutes for up to 240 minutes. Niacin was quantified by high-performance liquid chromatography. RESULTS: Ten out of the 12 inositol niacinate products were capsules and 6 of the 7 extended-release formulations were tablets. During the initial 30-minute dissolution study of inositol niacinate products, free niacin was released to various degrees. One product achieved fast dissolution, with >30% cumulative release of niacin. The cumulative percentage of niacin released at 240 minutes of all inositol niacinate products was statistically different (p < 0.0001). The majority of these products reached a plateau of releasing niacin in one to two hours, which was maintained until the end of the study. Six out of the seven extended-release niacin products had extended-release profiles. Five products showed a statistically higher dissolution rate (p < 0.05) than that of Niaspan. CONCLUSION: Significant variations in dissolution profiles were noted among the 7 nonprescription extended-release and 12 nonprescription inositol niacinate products in vitro, and their dissolution rates were not comparable to that of the prescription extended-release niacin. Further studies are warranted to correlate such dissolution data with their in vivo efficacy.

Delayed-Action Preparations↗