Modeling small-molecule release from PLG microspheres: effects of polymer degradation and nonuniform drug distribution

Raman, Chandrashekar; Berkland, Cory; Kim, Kyekyoon; Pack, Daniel W.

doi:10.1016/j.jconrel.2004.11.012

Cited by 148 publications

(159 citation statements)

References 19 publications

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“…As long polymer chains are broken into short chains, more and more 4 carboxylic and alcoholic end groups are generated. Meanwhile, water dissolves the drug particles, leading to a further increase in acidity.…”

Section: Model Developmentmentioning

confidence: 99%

A Mechanistic Model for Acidic Drug Release Using Microspheres Made of PLGA 50:50

Sevim

Pan

2016

Mol. Pharmaceutics

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Polyester microspheres are extensively studied for controlled release drug delivery devices, and many models have been developed to describe drug release from the bulk polymer.However, the interaction between drugs and polymers is ignored in most of the existing mathematical models. This paper presents a mechanistic model which captures the interplay between acidic drugs and bioresorbable polyesters. The model considers the autocatalytic effect on polymer degradation arising from carboxylic acid end groups of oligomers and drug molecules. Hence, the enhancing effect of acidic drug on the rate of degradation was fully considered. On the other hand the drug release from polyester microspheres is controlled by drug diffusion from polymer matrix. The drug diffusion coefficient depends strongly on the level of degradation of the polymer. This effect is also included in the model. It is shown that the model can effectively predict experimental data in the literature for both polymer degradation and drug release. Furthermore the model is used to design different systems of microspheres which release drugs with either a zero order profile or burst followed by zero order release profile.

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Section: Model Developmentmentioning

confidence: 99%

A Mechanistic Model for Acidic Drug Release Using Microspheres Made of PLGA 50:50

Sevim

Pan

2016

Mol. Pharmaceutics

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“…Much effort has been expended in predicting the loading and release of various drugs from polymeric microparticles [4]. In particular, modulating both the average size, size distribution, and the degradation rate of the microsphere allows control of the release kinetics, all other variables being the same [6][7][8][9]. A popular polymer used today is poly(D,L-lactic-co-glycolic acid) (PLGA), highly regarded for its safe biodegradability in the body and approval by the FDA.…”

Section: Introductionmentioning

confidence: 99%

NanoCipro encapsulation in monodisperse large porous PLGA microparticles

Arnold

Gorman

Schieber

et al. 2007

Journal of Controlled Release

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119

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Pulmonary drug delivery of controlled release formulations may provide an effective adjunct approach to orally delivered antibiotics for clearing persistent lung infections. Dry powder formulations for this indication should possess characteristics including; effective deposition to infected lung compartments, persistence at the infection site, and steady release of antibiotic. Large porous particles (∼10-15 μm) have demonstrated effective lung deposition and enhanced lung residence as a result of their large diameter and reduced clearance by macrophages in comparison to small microparticles (∼1-5 μm). In this report, Precision Particle Fabrication technology was used to create monodisperse large porous particles of poly(D,L-lactic-co-glycolic acid) (PLGA) utilizing oils as extractable porogens. After extraction, the resulting large porous PLGA particles exhibited a low density and a web-like or hollow interior depending on porogen concentration and type, respectively. Ciprofloxacin nanoparticles (nanoCipro) created by homogenization in dichloromethane, possessed a polymorph with a decreased melting temperature. Encapsulating nanoCipro in large porous PLGA particles resulted in a steady release of ciprofloxacin that was extended for larger particle diameters and for the solid particle morphology in comparison to large porous particles. The encapsulation efficiency of nanoCipro was quite low and factors impacting the entrapment of nanoparticles during particle formation were elucidated. A dry powder formulation with the potential to control particle deposition and sustain release to the lung was developed and insight to improve nanoparticle encapsulation is discussed.

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“…Most of the previous studies consider a variation of the diffusivity coefficient rather than the variation of particle size. As the degradation proceeds, the molecular weight decreases and the diffusivity coefficient increases, employing a bulk erosion system [31][32][33]. In the work reported here, the gradual change in size and particle morphology, see below, seems to suggest the co-existence of a surface erosion activity.…”

Section: Modelmentioning

confidence: 57%

“…The first part of release is commonly considered diffusion controlled [25,26,[31][32][33]. Also, in [34], it was shown that if the drug is water soluble, the release from erodible tablets follows primarily a swelling-controlled diffusion process.…”

Section: Modelmentioning

confidence: 99%

PLGA particle production for water-soluble drug encapsulation: Degradation and release behaviour

Gasparini

Holdich

Kosvintsev

2010

Colloids and Surfaces B: Biointerfaces

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Particles for subcutaneous depot use encapsulating a model water soluble drug have been produced from poly(lactic-glycolic acid) (PLGA) using a membrane emulsification -solvent evaporation technique. The release behaviour, mainly the change in size and inner morphology are reported.During release, the particles initially swelled in size, then reduced. A diffusion based model, taking in to account the change in particle size, is presented.Surface erosion is evident from the particle size and image evidence, and the diffusion model provides a fit to the data even during the surface erosion period, suggesting that the model drug diffuses before the particle degrades.

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Modeling small-molecule release from PLG microspheres: effects of polymer degradation and nonuniform drug distribution

Cited by 148 publications

References 19 publications

A Mechanistic Model for Acidic Drug Release Using Microspheres Made of PLGA 50:50

A Mechanistic Model for Acidic Drug Release Using Microspheres Made of PLGA 50:50

NanoCipro encapsulation in monodisperse large porous PLGA microparticles

PLGA particle production for water-soluble drug encapsulation: Degradation and release behaviour

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