Characterization of diffusion of macromolecules in konjac glucomannan solutions and gels by fluorescence recovery after photobleaching technique

Alvarez-Manceñido, Felipe; Braeckmans, Kevin; Smedt, Stefaan C. De; Demeester, Joseph; Landín, Mariana; Martínez‐Pacheco, Ramón

doi:10.1016/j.ijpharm.2006.02.029

Cited by 59 publications

(30 citation statements)

References 35 publications

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“…Irrespective of the type, molecular weight, chain length and their properties in solution, biopolymers have the ability to affect the passage of the drug into the fluid media in comparison to the transfer in the absence of polysaccharide. These results were in agreement with studies that demonstrated no dependence with polymer chain length (Berezhkovskii et al, 1999) but influence of the size of the diffusing probes (Alvarez-Manceñido et al, 2006). This study determined that it was diffusion through the polysaccharide polymer, not dissolution of atenolol particles that was limiting drug release based on the fact that solubility of atenolol was higher in 2.2% xanthan gum (30.3 ± 2.0 mg/mL) than in water (25.5 ± 1.1 mg/mL), while the diffusion coefficient was one order of magnitude lower in 2.2% xanthan gum (1.5 x 10 -10 m 2 /s) than without thickener (1.3 x 10 -9 m 2 /s).…”

Section: Discussionsupporting

confidence: 92%

“…However, although both modulus values (particularly G') and zero-shear viscosity increase as polysaccharide concentration increased, the lack of concomitant decrease in diffusion coefficient indicates that these rheological parameters are not useful indicators for restriction of drug movement. Similarly, rheology was not predictive for diffusivity of a fluorescent probe in mixtures of glucomannan and xanthan gum (Alvarez-Manceñido et al, 2006) and theophylline in scleroglucan gum solutions (Francois et al, 2005). Diffusion is reduced by increase in viscosity according to the Stokes-Einstein postulate (De Smedt et al, 1997) but only for diffusion of a perfect sphere through a fluid having the same bulk viscosity as the solvent (Cussler, 1997); measurement of microviscosity (or viscosity at the microscale) has been suggested to be a better indicator of resistance to diffusion by the media surrounding the drug molecule (AlvarezLorenzo et al, 1999).…”

Section: Discussionmentioning

confidence: 96%

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Understanding the mechanism of drug delivery from thickened fluids to aid swallowing of medications

Torres¹,

Juliana²

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Medications are often crushed and mixed with foods or fluids to aid drug delivery for those who cannot or prefer not to swallow whole tablets or capsules. Dysphagic patients have the added problem of being unable to safely swallow fluids, so thickeners are added to ensure safe swallowing. These thickened fluids are then also used to deliver crushed medications in replacement of water. This thesis explores the influence of thickened water co-administration on drug release in gastric fluid, the effect of rheological properties of these agents and their contribution to describing the mechanism of release. The literature review (Chapter 1) examines oral dosage form administration, rheological properties of these agents as a means to ensure medication delivery and mechanisms of drug release. It is highlighted that thickened fluids have the potential to alter drug release but prediction of the effect of co-administration is not currently reported.Chapter 2 investigates the delivery of medications with thickened fluids as an indicator for potential compromise of drug bioavailability. In vitro dissolution in simulated gastric fluid is investigated for crushed atenolol immediate release tablets mixed with thickened fluids. Five commercial viscosityincreasing agents of varied polysaccharide composition are used at three thickness levels prescribed for dysphagic patients (levels 150, 400, 900). All types of thickening agents are non-Newtonian shear thinning fluids. The greatest thickness (level 900) significantly restricts dissolution, and products that are primarily based on xanthan gum also significantly delay dissolution at the intermediate thickness level (level 400). The interactions of the polysaccharide chains, particularly the rigid rod type conformation of xanthan gum, traps drug molecules within it resulting in impaired dissolution. Under the conditions of this experiment, the higher concentrations of thickening agents remain in large lumps rather than disintegrating into the media. Drug release is generally affected to a greater extent by high-viscosity fluids than low-viscosity fluids at 50 s -1 , but viscosity at this single shear rate of 50 s -1 is not a good indicator for effect on drug dissolution because viscosity changes with shear rate. The determination of other rheological parameters such as viscoelasticity and the effect of breaking up of the structures may be required.To investigate whether it is possible to improve drug release from thickened fluids, in Chapter 3 the effect of the state of aggregation of the active ingredient with thickened fluids is investigated.Paracetamol is the model drug because it is available in a range of formulations with the drug in solution (elixir, dissolved effervescent tablet) or dispersion (suspension). Xanthan gum, which causes the greatest restriction on dissolution (Chapter 2), is used at level 900 as the thickener.ii Crushed tablets with thickener are prepared using manual (i.e. the standard method in clinical practice) or mechanical mixing. The unthickene...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 96%

Understanding the mechanism of drug delivery from thickened fluids to aid swallowing of medications

Torres¹,

Juliana²

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“…Using a suitable FRAP model, analysis of the fluorescence recovery can yield the physical quantities describing the local diffusion in the sample, such as the diffusion coefficient in case of free diffusion. FRAP has become a popular technique to study the diffusion of molecules in a variety of systems like cell membranes [1][2][3], polymer gel systems [4][5][6][7][8][9] and living cells [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Straightforward FRAP for quantitative diffusion measurements with a laser scanning microscope

et al. 2010

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Confocal or multi-photon laser scanning microscopes are convenient tools to perform FRAP diffusion measurements. Despite its popularity, accurate FRAP remains often challenging since current methods are either limited to relatively large bleach regions or can be complicated for non-specialists. In order to bring reliable quantitative FRAP measurements to the broad community of laser scanning microscopy users, here we have revised FRAP theory and present a new pixelbased FRAP method relying on the photobleaching of rectangular regions of any size and aspect ratio. The method allows for fast and straightforward quantitative diffusion measurements due to a closed-form expression for the recovery process utilising all available spatial and temporal data. After a detailed validation, its versatility is demonstrated by diffusion studies in heterogeneous biopolymer mixtures. 2010 Optical Society of America

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“…FRAP was used to quantify the diffusion of guar oligomer inside the hydrogel, showing that diffusion was decreased significantly compared to non-interacting probes and remained constant over a couple of hours, resulting in a gradual release. Another system intended for colonic drug delivery is a hydrogel based on konjac glucomannan, which is a polysaccharide that is not degradable in the small intestine but is degradable by anaerobic human intestinal bacteria (56). FRAP was performed to measure the diffusion and mobile fraction of dextrans in the system and it was found that the diffusion behaviour cannot only be explained by macroscopic properties of the medium.…”

Section: Diffusion Inside Hydrogelsmentioning

confidence: 99%

FRAP in Pharmaceutical Research: Practical Guidelines and Applications in Drug Delivery

et al. 2013

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Fluorescence recovery after photobleaching (FRAP) is a fluorescence microscopy technique that has attracted a lot of interest in pharmaceutical research during the last decades. The main purpose of FRAP is to measure diffusion on a micrometer scale in a non-invasive and highly specific way, making it capable of measurements in complicated biomaterials, even in vivo. This has proven to be very useful in the investigation of drug diffusion inside different tissues of the body and in materials for controlled drug delivery. FRAP has even found applications for the improvement of several medical therapies and for the field of diagnostics. In this review, an overview is given of the different applications of FRAP in pharmaceutical research, together with essential guidelines on how to perform and analyse FRAP experiments.

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Characterization of diffusion of macromolecules in konjac glucomannan solutions and gels by fluorescence recovery after photobleaching technique

Cited by 59 publications

References 35 publications

Understanding the mechanism of drug delivery from thickened fluids to aid swallowing of medications

Understanding the mechanism of drug delivery from thickened fluids to aid swallowing of medications

Straightforward FRAP for quantitative diffusion measurements with a laser scanning microscope

FRAP in Pharmaceutical Research: Practical Guidelines and Applications in Drug Delivery

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