A dissolution‐diffusion model for the TAXUS™ drug‐eluting stent with surface burst estimated from continuum percolation

Abstract

A two-layer dissolution-diffusion model is derived which incorporates a surface burst component that is estimated from continuum percolation models of overlapping Poisson distributed spheres. The model is shown to adequately describe the release properties of paclitaxel from a hydrophobic polymer matrix, including the surface burst and sustained release dependence on drug loading.

Stent elution rate determines drug deposition and receptor-mediated effects

“…Subsequently, imaging studies of CYPHER ® Stent coatings [20,21] and similar conformal coated DES [22–24] explained that drug distribution can deviate from the idealized layered designs due to the influence of mixing and drying that occurs during coating manufacture. Specifically, images of the coatings revealed significant concentrations of dispersed drug in the top-coat [21,24–26] that are inconsistent with the reservoir/membrane description and explain observations of early drug bursts from CYPHER ® Stents and other conformal coated stents[5,24,27]. In light of these studies, we idealize CYPHER ® Stent coatings as monolithic films that contain two pools of dispersed drug, one that is surface-connected and elutes through a percolating network of drug filled pores, and another that is embedded within the matrix and diffuses more slowly through the percolating polymer phase.…”

“…Following Hossainy and Prabhu [5] we assumed that elution of the surface-connected pool of drug is governed by diffusion; and as its elution is fast relative to the elution of the second drug pool, we invoked the late time approximation [28] and modeled cumulative elution of surface enriched drug as a first-order process. Following Barocas et al [27] we assumed that elution of the matrix-embedded pool of drug follows Higuchi-type diffusion-limited dissolution kinetics [29]. Thus, cumulative sirolimus elution kinetics from CYPHER ® Stent coatings were parameterized as $$M_{italic\text{stent}}\left(0\right)-M_{italic\text{stent}}\left(t\right)=M_{\mathrm{italicfo}}true(1-e^{-K_{\mathrm{italicfo}}t}true)+Q_{\mathrm{italicsus}}\sqrt{t}$$ where M stent (0) denotes the initial load of drug per stent (μg), M fo is the initial pool of first order eluting drug (μg) with rate constant K fo (d −1 ), and Q sus (μg·d −1/2 ) is the Higuchi rate constant.…”

Pore Networks and Polymer Rearrangement on a Drug-Eluting Stent as Revealed by Correlated Confocal Raman and Atomic Force Microscopy

“…Several techniques have been used to study the physical and chemical properties of DES. Confocal Raman microscopy imaging has been used to characterize DES coatings qualitatively and quantitatively, taking advantage of the depth profiling ability of CRM in imaging transparent coatings. − Mass spectrometry techniques such as cluster and secondary ion mass spectrometry (SIMS) have also provided chemical depth profiles of DES coatings. ,− Atomic force microscopy and scanning electron microscopy (SEM) have been used for the study of the drug elution process and coating integrity in DES coatings. ,,− Within several of these references, the researchers use a combination of methods to study a particular parameter such as drug–polymer formulation, processing, or in vitro conditions and relate these properties to product performance. In many instances, device surrogates such as thin films or flat metallic coupons rather than the actual devices are used because of instrumental constraints.…”

Portable Nanocomposite System for Wound Healing in Space

“…Then, a sustained and prolonged drug release is requested to promote healing. The kinetics of the burst release of the drug, in perfect sink conditions, can be described as initial dissolution followed by a fast diffusion from clusters to the contiguous media of overlapping drug particles deposited on the surface [ 48 ]. The burst release is principally produced by the drug adsorbed in the pores on the surface of cryogels during the loading process [ 49 ].…”