Examination of drug release and distribution from drug-eluting stents with a vessel-simulating flow-through cell

Seidlitz, Anne; Nagel, Stefan; Semmling, Beatrice; Grabow, Niels; Martin, H.; Senz, Volkmar; Harder, Claus; Sternberg, Katrin; Schmitz, Klaus‐Peter; Kroemer, Heyo K.

doi:10.1016/j.ejpb.2010.12.021

Cited by 38 publications

(35 citation statements)

References 37 publications

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“…Alternatively, the spatial distribution in the hydrogel can be examined using the vessel-simulating flow-through cell if microscopically detectable model substances, such as fluorescent dyes, are released from the stent. A detailed description of how alginate cross-sections and alginate films lining the lumen can be prepared and examined is given elsewhere (35). Using these techniques, distribution depth and spatial distribution in relation to the distance from the areas of stent contact can be visualized.…”

Section: Apparatus Design and Experimental Conditionsmentioning

confidence: 99%

Biorelevant Dissolution Testing of Drug-Eluting Stents: Experiences with a Modified Flow-Through Cell Setup

Seidlitz¹,

Nagel²,

Semmling³

et al. 2011

Dissolution Technol.

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In vitro dissolution testing of drug-eluting stents (DES) poses a special challenge in terms of apparatus design due to the very specialized local treatment of the vessel wall in the immediate vicinity of the blood flowing through the vessel and the stent lumen. A vessel-simulating flow-through cell was designed to emulate the placement of a DES in vivo and the flow through the lumen in a simplified in vitro setup, which also allows for the examination of distribution processes. The method is based on the compendial flow-through cell apparatus (USP 4), which was modified by the addition of a hydrogel compartment that represents the vessel wall and the adaptation of the flow rate to the blood flow rate in the coronary vessels. A comparison of the dissolution and release results obtained with the vessel-simulating flow-through cell with standard paddle (USP 2) and flow-through cell (USP 4) apparatus methods shows that release from the coating was decelerated by embedding in the hydrogel in the adapted apparatus. Further experiments with both hydrophilic and hydrophobic fluorescent model compounds coated onto the stents were performed to investigate the effects of different method parameters and variations in the coating composition. While release and distribution of hydrophilic fluorescein sodium were dependent on the flow rate and implantation technique, release kinetics of hydrophobic triamterene were influenced by the coating thickness and the model substance content of the coating. These results illustrate the importance of choosing the correct apparatus design and test parameters adapted to biorelevant conditions for specialized dosage forms such as DES.

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Section: Apparatus Design and Experimental Conditionsmentioning

confidence: 99%

Biorelevant Dissolution Testing of Drug-Eluting Stents: Experiences with a Modified Flow-Through Cell Setup

Seidlitz¹,

Nagel²,

Semmling³

et al. 2011

Dissolution Technol.

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“…In vitro perfusion systems represent possible opportunities to overcome the limitations connected with standard release methods. One example for such a system is the vessel-simulating flow-through cell developed by Seidlitz et al [1]. This vessel-simulating flow-through cell allows examining the release and distribution of pharmaceuticals from DES independent of animal models under standardised dissolution testing by the use of hydrogel-based matrices serving as an alternative to tissue.…”

Section: Introductionmentioning

confidence: 99%

Investigation of in Vitro Drug Release Behaviour of Drug-Eluting Stents Using a Perfusion Culture System

Rudolph

Eickner

Seidlitz

et al. 2013

Biomedical Engineering / Biomedizinische Technik

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“…They are used for cell encapsulation [8], tissue engineering [9] and in controlled release dosage forms [10,11]. Recently, hydrogels have been used for biorelevant dissolution testing of dosage forms which are injected or implanted into tissue [12][13][14][15][16] to simulate some properties of the tissue surrounding the drug delivery systems such as drug transport via diffusion. Whereas convective drug transport dominates in fully-agitated dissolution test setups diffusion is the predominant mechanism of drug transport in hydrogels.…”

Section: Introductionmentioning

confidence: 99%

“…The vessel-simulating flow-through cell (vFTC) [14,16] has been developed in order to examine drug release and distribution from drug-eluting stents (DES) under conditions adapted to some of the aspects of the in vivo stent placement. The vFTC is based on the compendial flow-through cell which is described in the respective Pharmacopeias.…”

Section: Introductionmentioning

confidence: 99%

Long-term stable hydrogels for biorelevant dissolution testing of drug-eluting stents

Semmling¹,

Nagel²,

Sternberg³

et al. 2013

J Pharm Technol Drug Res

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Background: For the purpose of biorelevant dissolution testing hydrogels have recently been used to investigate release and distribution behavior of drugs released from specialized dosage forms such as drug-eluting stents. For stent testing using the vesselsimulating flow-through cell (vFTC) certain functional properties regarding life time of the used hydrogels such as hardening/ softening, degradation/erosion and swelling/shrinkage during the time period of dissolution testing are of highest interest. Methods: Hydrogels composed of alginate, agar, agarose, polyacrylamide (PAA) and poly(vinyl alcohol) (PVA) were prepared using physical and chemical cross-linking methods. To characterize the mechanical stability of the test specimens stress-strain curves were recorded by texture analysis before and after perfusion in the vFTC for 28 days and Young's moduli were calculated. The surface morphology of the test specimens was examined using scanning electron microscopy. Water uptake upon incubation was determined. Results: Besides the previously established alginate gels, suitable hydrogels consisting of 2 wt% agar, 2 wt% agarose, 10 wt% PAA or 15 wt% PVA were identified. Comparison of stress-strain curves indicated a sample softening of reference as well as agar and a slight hardening of PVA whereas hardness of agarose and PAA remained unchanged. Young's moduli of agarose and PAA were almost unaffected after 28 days of perfusion. Swelling of PAA by 18 wt% and shrinkage of PVA by 14 wt% was observed compared to agar and agarose whose water uptake was negligibly small. Conclusion:The hydrogels differ not only in their preparation procedure but also regarding their swelling properties, surface morphology and texture. Due to the ease of handling, mild gelling conditions, no swelling tendencies, elastic properties, and nearly unaffected texture after 28 days of perfusion compared to native test specimens, agarose gels are considered as the best choice for longterm testing using the vFTC.

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Examination of drug release and distribution from drug-eluting stents with a vessel-simulating flow-through cell

Cited by 38 publications

References 37 publications

Biorelevant Dissolution Testing of Drug-Eluting Stents: Experiences with a Modified Flow-Through Cell Setup

Biorelevant Dissolution Testing of Drug-Eluting Stents: Experiences with a Modified Flow-Through Cell Setup

Investigation of in Vitro Drug Release Behaviour of Drug-Eluting Stents Using a Perfusion Culture System

Long-term stable hydrogels for biorelevant dissolution testing of drug-eluting stents

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