A mechanistic model of controlled drug release from polymer millirods: effects of excipients and complex binding.

A mechanistic model of controlled drug release from polymer millirods: effects of excipients and complex binding. Research Abstract Details 

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A mechanistic model of controlled drug release from polymer millirods: effects of excipients and complex binding. Abstract Text:

Fangjing Wang,Gerald M Saidel,Jinming Gao,

The incorporation of different cyclodextrin (CD) excipients such as HPbeta-CD, beta-CD, gamma-CD or alpha-CD into polymer millirods for complexing beta-lapachone (beta-lap), a potent anti-cancer drug, significantly improved the drug release kinetics with various drug release patterns. However, such a complex system requires a mechanistically based model in order to provide a quantitative understanding of the many molecular events and processes that are essential for the rational development of millirod implants. This study focuses on mathematical modeling of drug release from PLGA cylindrical millirods. This millirod system incorporates multiple components: a PLGA matrix; excipient in free and complex forms; drug in free, bound, and crystalline forms. The model characterizes many dynamic transport and complexation processes that include radial diffusion, excipient complexation and crystalline drug dissolution. Optimal estimates of the model parameters were obtained by minimizing the difference between model simulation and experimentally measured drug release kinetics. The effects of different drug loadings on the drug release rate were simulated and compared with other data to validate this model. Whereas our model can simulate all the experimental data, the Higuchi model can simulate only some of them. Furthermore, our model incorporates mechanisms by which the processes underlying drug release from a polymer matrix can be quantitatively analyzed. These processes include drug entrapment/dissolution in the matrix, drug recrysallization, and supersaturation. This modeling study shows that complex binding capacity, which affects drug initial conditions, drug-polymer interactions, and bound drug behavior in aqueous solution, is crucial in controlling drug release kinetics.

A mechanistic model of controlled drug release from polymer millirods: effects of excipients and complex binding. Publishing Authors By Initials

F Wang,GM Saidel,J Gao,

For similar macromolecular substances: polymers research abstracts see: macromolecular substances: polymers research

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MEDLINE DATE:

A mechanistic model of controlled drug release from polymer millirods: effects of excipients and complex binding. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of controlled release : official journal o

VOLUME: 119

Page Numbers: 111-20

Journal Abbreviation:

ISSN: 1873-4995

DAY: 9

MONTH: 02

YEAR: 2007

A mechanistic model of controlled drug release from polymer millirods: effects of excipients and complex binding. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8607908

A mechanistic model of controlled drug release from polymer millirods: effects of excipients and complex binding. Keywords Mesh Terms:

KEYWORDS: Polymers

MESH TERMS: pharmacokinetics

Chemical & Substance for Abstract: A mechanistic model of controlled drug release from polymer millirods: effects of excipients and complex binding. Information

Substance Name: Polymers

Registry Number: 0

Grant and Affiliation Information for A mechanistic model of controlled drug release from polymer millirods: effects of excipients and complex binding.

AFFILIATION: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106-7207, United States.

Country: Netherlands

AGENCY: United States NCI

GRANT: R01 CA90696

ACRONYM: CA

MEDLINETA: J Control Release

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