A mechanistic modelling approach to polymer dissolution using magnetic resonance microimaging

Kaunisto, Erik; Abrahmsén-Alami, Susanna; Borgquist, Per; Larsson, Anette; Nilsson, Bernt; Axelsson, Anders

doi:10.1016/j.jconrel.2010.07.102

Cited by 43 publications

(13 citation statements)

References 26 publications

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“…The controlled drug release from hydrogels is an important issue for medical applications that has been under intensive investigation in the last decades, both experimentally (Hoare and Kohane, 2008;Ratner and Hoffman, 1976) or through mathematical modelling (Peppas and Khare, 1993;Siepmann and Siepmann, 2008), including empirical/semi-empirical models, as well as mechanistic realistic ones (Caccavo et al, 2015a(Caccavo et al, , 2015bKaunisto et al, 2010;Lamberti et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Controlled drug release from hydrogels for contact lenses: Drug partitioning and diffusion

Pimenta

Ascenso

Fernandes

et al. 2016

International Journal of Pharmaceutics

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Optimization of drug delivery from drug loaded contact lenses assumes understanding the drug transport mechanisms through hydrogels which relies on the knowledge of drug partition and diffusion coefficients. We chose, as model systems, two materials used in contact lens, a poly-hydroxyethylmethacrylate (pHEMA) based hydrogel and a silicone based hydrogel, and three drugs with different sizes and charges: chlorhexidine, levofloxacin and diclofenac. Equilibrium partition coefficients were determined at different ionic strength and pH, using water (pH 5.6) and PBS (pH 7.4). The measured partition coefficients were related with the polymer volume fraction in the hydrogel, through the introduction of an enhancement factor following the approach developed by the group of C. J. Radke (Kotsmar et al., 2012;Liu et al., 2013). This factor may be decomposed in the product of three other factors , and which account for, respectively, hard-sphere size exclusion, electrostatic interactions, and specific solute adsorption. While and are close to 1, >>1 in all cases suggesting strong specific interactions between the drugs and the hydrogels. Adsorption was maximal for chlorhexidine on the silicone based hydrogel, in water, due to strong hydrogen bonding.The effective diffusion coefficients, , were determined from the drug release profiles.Estimations of diffusion coefficients of the non-adsorbed solutes = × allowed comparison with theories for solute diffusion in the absence of specific interaction with the polymeric membrane.

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Section: Introductionmentioning

confidence: 99%

Controlled drug release from hydrogels for contact lenses: Drug partitioning and diffusion

Pimenta

Ascenso

Fernandes

et al. 2016

International Journal of Pharmaceutics

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“…To describe the water concentration dependence of the diffusion coefficients we used a Fujita dependence [28], which is based on a free volume approach. This type of model has been successfully used to model drug diffusion in hydroxypropyl methylcellulose (HPMC) [29, 30], polymer diffusion in polyethylene oxide (PEO) [31] and other similar systems [32–34]. In this approach, diffusion coefficients are dependent on the water concentration according to Eq.…”

Section: Methodsmentioning

confidence: 99%

Controlling the hydration rate of a hydrophilic matrix in the core of an intravaginal ring determines antiretroviral release

Teller

Malaspina

Rastogi

et al. 2016

Journal of Controlled Release

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Intravaginal ring technology is generally limited to releasing low molecular weight species that can diffuse through the ring elastomer. To increase the diversity of drugs that can be delivered from intravaginal rings, we designed an IVR that contains a drug matrix encapsulated in the core of the IVR whereby the mechanism of drug release is uncoupled from the interaction of the drug with the ring elastomer. We call the device a flux controlled pump, and is comprised of compressed pellets of a mixture of drug and hydroxypropyl cellulose within the hollow core of the ring. The pump orifice size and chemistry of the polymer pellets control the rate of hydration and diffusion of the drug-containing hydroxypropyl cellulose gel from the device. A mechanistic model describing the hydration and diffusion of the hydroxypropyl cellulose matrix is presented. Good agreement between the quantitative model predictions and the experimental studies of drug release was obtained. We achieved controlled release rates of multiple antiretrovirals ranging from µg/day to mg/day by altering the orifice design, drug loading, and mass of pellets loaded in the device. This device could provide an adaptable platform for the vaginal drug delivery of many molecules.

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“…Kaunisto et al developed a mechanistic model (in 2010 for the dissolution of pure poly(ethylene oxide) tablets [111], extended in 2013 [112] to HPMC matrices loaded with a poorly soluble drug) to analyze the drug release behavior in swellable systems. In this model (considered at constant density), the polymer mass fraction description was coupled with the transport equations for drug and water through the mass fraction constraint (Table 3 equations (E-F) with (v mix ) → 0), therefore overcoming the Lamberti model 2° drawback.…”

Section: Multicomponent Approach: Mass Transfermentioning

confidence: 99%

Swellable Hydrogel-based Systems for Controlled Drug Delivery

Caccavo¹,

Cascone²,

Lamberti³

et al. 2016

Smart Drug Delivery System

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The controlled delivery of drugs can be effectively obtained using systems based on hydrogels. Tablets, to be orally administered, represent the simplest and the most traditional dosage systems based on hydrogel. Their formulation and preparation require to mix and to compress, in proper ratios, various excipients, including a swellable polymer and a drug. Carriers for controlled release systems are usually cross-linked polymers able to form hydrogels that show peculiar release mechanisms, where both diffusion and tablet swelling play important roles.When a dry swellable hydrogel-based matrix is immersed in a physiological fluid, this starts to penetrate inside the polymeric hydrophilic matrix. When a certain solvent concentration is reached, the polymeric chains unfold due to a glass-rubber transition, and a gel-like layer is formed. In the swollen region, the drug molecules can easily diffuse toward the outer dissolution medium, once they are dissolved. The polymer network became extremely hydrated where the swollen matrix is in contact with the outer medium, and processes like chain disentanglement take place, "eroding" the matrix.This chapter is focused on the analysis of the state of the art about the uses of carriers for controlled release systems composed by hydrogel-based matrices. This analysis has been performed studying in deep both the experimental and the modeling techniques which have been investigated over the years to characterize all the phenomena involved during the drug release.

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A mechanistic modelling approach to polymer dissolution using magnetic resonance microimaging

Cited by 43 publications

References 26 publications

Controlled drug release from hydrogels for contact lenses: Drug partitioning and diffusion

Controlled drug release from hydrogels for contact lenses: Drug partitioning and diffusion

Controlling the hydration rate of a hydrophilic matrix in the core of an intravaginal ring determines antiretroviral release

Swellable Hydrogel-based Systems for Controlled Drug Delivery

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