Development of a vessel-simulating flow-through cell method for the in vitro evaluation of release and distribution from drug-eluting stents

Drug-eluting stents implanted in blood vessels are subject to various dynamics of blood flow. In this study, we present the evaluation of a mathematical model considering the effect of flow rate, to simulate the kinetic profiles of drug release (Diclofenac Sodium (DS)) from in-vitro from PLGA films. This model solves a set of non-linear equation for modeling simultaneously the burst, diffusion, swelling and erosion involved in the mechanisms of liberation. The release parameters depending on the flow rate are determined using the corresponding mathematical equations. For the evaluation of the proposed model, test data obtained in our laboratory are used. To quantify DS release from drug-carrier PLGA films, we used the flow-through cell apparatus in a closed-loop. Four flow rate values are applied. For each value, the model-substance liberation kinetics showed an increase in drug released with the flow rate. The simulated release profiles show good agreement with the experimental results. Therefore, the use of this model could provide a practical tool to assess in-vitro drug release profiles from polymer matrices under continuous flow rate constraint, and could help improve the design of drug eluting stents.

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Sustained drug release using cobalt oxide nanowires for the preparation of polymer-free drug-eluting stents

Journal of Biomaterials Applications ◽

10.1177/0885328218792141 ◽

2018 ◽

Vol 33 (3) ◽

pp. 352-362 ◽

Cited By ~ 2

Author(s):

Tarek M Bedair ◽

Il Jae Min ◽

Wooram Park ◽

Yoon Ki Joung ◽

Dong Keun Han

Keyword(s):

Drug Release ◽

Cobalt Oxide ◽

Drug Eluting Stents ◽

Therapeutic Drug ◽

Burst Release ◽

Release Behavior ◽

Cobalt Chromium ◽

Oxide Nanowires ◽

Drug Eluting

Polymer-based drug-eluting stents (DESs) represented attractive application for the treatment of cardiovascular diseases; however, polymer coating has caused serious adverse responses to tissues such as chronic inflammation due to acidic by-products. Therefore, polymer-free DESs have recently emerged as promising candidates for the treatment; however, burst release of drug(s) from the surface limited its applications. In this study, we focused on delivery of therapeutic drug from polymer-free (or -less) DESs through surface modification using cobalt oxide nanowires (Co3O4 NWs) to improve and control the drug release. The results demonstrated that Co3O4 NWs could be simply fabricated on cobalt–chromium substrate by ammonia-evaporation-induced method. The Co3O4 NWs were uniformly arrayed with diameters of 50–100 nm and lengths of 10 µm. It was found that Co3O4 NWs were comparatively stable without any delamination or change of the morphology under in vitro long-term stability using circulating system. Sirolimus was used as a model drug for studying in vitro release behavior under physiological conditions. The sirolimus release behavior from flat cobalt–chromium showed an initial burst (over 90%) after one day. On the other hand, Co3O4 NWs presented a sustained sirolimus release rate for up to seven days. Similarly, the polymer-less specimens on Co3O4 NWs substrates sustained sirolimus release for a longer-period of time when compared to flat Co–Cr substrates. In summary, the current approach of using Co3O4 NWs-based substrates might have a great potential to sustain drug release for drug-eluting implants and medical devices including stents.

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An In Vitro Evaluation of Four Types of Drug-Eluting Microspheres Loaded with Doxorubicin

Journal of Vascular and Interventional Radiology ◽

10.1016/j.jvir.2016.05.015 ◽

2016 ◽

Vol 27 (9) ◽

pp. 1425-1431 ◽

Cited By ~ 31

Author(s):

Thierry de Baere ◽

Stephen Plotkin ◽

Renee Yu ◽

Allison Sutter ◽

Yue Wu ◽

...

Keyword(s):

In Vitro Evaluation ◽

Drug Eluting

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INFLUENCE OF DOSE AND USP DISSOLUTION APPARATUS IN THE RELEASE PERFORMANCE OF REFERENCE TABLETS: PROPRANOLOL-HCl AND RANITIDINE-HCl CASES

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2019v11i4.33293 ◽

2019 ◽

pp. 164-170

Author(s):

JOSE RAUL MEDINA-LOPEZ ◽

LUIS ANTONIO CEDILLO-DIAZ ◽

MARCELA HURTADO

Keyword(s):

In Vitro Dissolution ◽

Dissolution Time ◽

Reference Drug ◽

Cell Method ◽

Drug Products ◽

Propranolol Hcl ◽

Flow Through ◽

Dissolution Apparatus ◽

Paddle Apparatus

Objective: Due to quality of generic formulations depends on available information of reference drug products the aim of this work was to perform an in vitro dissolution study of two doses of propranolol-HCl and ranitidine-HCl reference tablets using USP basket or paddle apparatus and flow-through cell method. Methods: Two doses of propranolol-HCl (10-mg and 80-mg) and ranitidine-HCl (150-mg and 300-mg) of Mexican reference products were used. Dissolution profiles of propranolol-HCl were obtained with USP basket apparatus at 100 rpm and 1000 ml of 1% hydrochloric acid. Profiles of ranitidine-HCl were determined with USP paddle apparatus at 50 rpm and 900 ml of distilled water. All formulations were also studied with the flow-through cell method using laminar flow at 16 ml/min. Dissolution profiles were compared by model-independent (f2 similarity factor, mean dissolution time and dissolution efficiency) and model-dependent methods (dissolution data adjusted to some mathematical equations). Time data, derived from these adjustments, as t50%, t63.25%, and t85% were used to compare dissolution profiles. Results: With all approaches used and being high solubility drugs significant differences were found between low and high doses and between USP dissolution apparatuses (*P<0.05). Conclusion: In vitro dissolution performance of two doses of propranolol-HCl and ranitidine-HCl was not expected. Considering the same USP dissolution apparatus, the reference tablets did not allow the simultaneous release of the used doses. The results could be of interest for pharmaceutical laboratories or health authorities that classify some drug products as a reference to be used in dissolution and bioequivalence studies.

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

Biomedical Engineering / Biomedizinische Technik ◽

10.1515/bmt-2013-4098 ◽

2013 ◽

Cited By ~ 1

Author(s):

A Rudolph ◽

T Eickner ◽

A Seidlitz ◽

W Weitschies ◽

A Wree ◽

...

Keyword(s):

Drug Release ◽

Culture System ◽

Perfusion Culture ◽

Drug Eluting Stents ◽

In Vitro Drug Release ◽

Drug Eluting

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Flow-Mediated Drug Transport from Drug-Eluting Stents is Negligible: Numerical and In-vitro Investigations

Annals of Biomedical Engineering ◽

10.1007/s10439-018-02176-y ◽

2018 ◽

Vol 47 (3) ◽

pp. 878-890 ◽

Cited By ~ 2

Author(s):

Pujith R. S. Vijayaratnam ◽

John A. Reizes ◽

Tracie J. Barber

Keyword(s):

Drug Transport ◽

Drug Eluting Stents ◽

Drug Eluting

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Comparison of overexpansion capabilities and thrombogenicity at the side branch ostia after implantation of four different drug eluting stents

Scientific Reports ◽

10.1038/s41598-020-75836-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Pawel Gasior ◽

Shengjie Lu ◽

Chen Koon Jaryl Ng ◽

Wee Yee Daniel Toong ◽

En Hou Philip Wong ◽

...

Keyword(s):

Shear Rate ◽

Focal Point ◽

Biomechanical Properties ◽

Side Branch ◽

Drug Eluting Stents ◽

Drug Eluting ◽

Electron Microscope Analysis ◽

Bifurcation Lesions ◽

Stent Diameter

AbstractInterventions in bifurcation lesions often requires aggressive overexpansion of stent diameter in the setting of long tapering vessel segment. Overhanging struts in front of the side branch (SB) ostium are thought to act as a focal point for thrombi formation and consequently possible stent thrombosis. This study aimed to evaluate the overexpansion capabilities and thrombogenicity at the SB ostia after implantation of four latest generation drug-eluting stents (DES) in an in-vitro bifurcation model. Four clinically available modern DES were utilized: one bifurcation dedicated DES (Bioss LIM C) and three conventional DES (Ultimaster, Xience Sierra, Biomime). All devices were implanted in bifurcation models with proximal optimization ensuring expansion before perfusing with porcine blood. Optical coherence tomography (OCT), immunofluorescence (IF) and scanning electron microscope analysis were done to determine thrombogenicity and polymer coating integrity at the over-expanded part of the stents. Computational fluid dynamics (CFD) was performed to study the flow disruption. OCT (p = 0.113) and IF analysis (p = 0.007) demonstrated lowest thrombus area at SB ostia in bifurcation dedicated DES with favorable biomechanical properties compared to conventional DES. The bifurcated DES also resulted in reduced area of high shear rate and maximum shear rate in the CFD analysis. This study demonstrated numerical differences in terms of mechanical properties and acute thrombogenicity at SB ostia between tested devices.

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