Evaluation of the suitability of a fluidized bed process for the coating of drug-eluting stents.

Drug-eluting stents are often coated using single-stent coating techniques. In pharmaceutical industry, single-tablet coating is unthinkable. Instead large batches of tablets are coated in fluidized bed apparatuses or pan coaters. Therefore, it was the aim of this work to evaluate whether stents can be coated using a fluidized bed process. For this purpose stents were coated with the model fluorescent drug triamterene embedded in ammonium methacrylate copolymer. Different stent lengths as well as different coating yields were assessed and also a drug-free topcoat was evaluated. The coated stents were analysed regarded coating layer mass, drug content, surface structure, coating thickness and drug release. Furthermore, coating yield and stent defect rate were examined. Except for one stent configuration good results were obtained without optimization of process parameters which indicates the suitability of the method to coat large amounts of stents simultaneously in principle. Drug release was tuneable over a wide range of time spans and a wide range of drug loadings was produced. Further work will be necessary to transform the results of this study from a model stent to a clinically relevant product.

Influence of Dissolution Vessel Geometry and Dissolution Medium on In Vitro Dissolution Behaviour of Triamterene-Coated Model Stents in Different Test Setups.

The aim of this study was to investigate if the geometry of the dissolution vessel, the dissolution medium volume and composition might contribute to the variation in drug release from drug-eluting stents (DES) in different test setups, which has been observed in previous in vitro studies. Therefore, DES containing triamterene as model substance were produced via fluidised-bed technology. Dissolution testing was carried out using different incubation setups, the reciprocating holder (USP Apparatus 7) and two flow-through methods, a method similar to the USP Apparatus 4 (FTC) and the vessel-simulating flow-through cell (vFTC) equipped with a hydrogel as a second compartment simulating the blood vessel wall. The results indicate that dissolution vessel geometry and medium volume had no influence on the release behaviour and only the flow-through cell methods yielded a lower dissolution rate than the incubation setups (80.6 ± 2.0% released in the FTC after 14 days compared to > 90% for all incubation setups). The composition of the hydrogel used in the vFTC also affected the dissolution rate (53.9 ± 4.5% within 14 days with a hydrogel based on phosphate-buffered saline compared to 78.2 ± 1.2% obtained with a hydrogel based on water) possibly due to different solubility of triamterene in the release media as well as interactions between the coating polymer and the release medium. Hence, the introduction of a hydrogel as a second compartment might lead to a more biorelevant test setup.

Controlling drug delivery from coronary stents: are we aiming for the right targets?

In this review article, the currently employed or explored delivery concepts for local intravascular drug delivery with drug-eluting stents (DES) are discussed with a special emphasis on clinical evidence regarding the desired release profiles. Traditional concepts to control drug release from DES include diffusion through polymers, polymer degradation and erosion as well as dissolution of particulate drug. Published clinical studies do not always reveal fine mechanistic details. The long duration of release favored for DES and the short duration of release favored for drug-eluting balloons require further investigation in experimental studies and clinical trials.