Degradation and adhesive/cohesive strengths of a reservoir-based drug eluting stent.

This paper presents the results of loss of mechanical strengths due to the degradation that occurs in a model reservoir-based coronary stent, the NEVO(™) Sirolimus-eluting Stent (NEVO(™) SES). The adhesion of the formulation to the reservoir and cohesion within the formulation in the time course of hydrolysis were determined using a micro-testing system that was developed specifically for the measurements of the adhesive and cohesive strengths of suspended polymeric films. The strengths were measured after hydration, during degradation with gentle agitation, as well as degradation with pulsatile mechanical loading.

Pore networks and polymer rearrangement on a drug-eluting stent as revealed by correlated confocal Raman and atomic force microscopy.

Drug release from and coating morphology on a CYPHER sirolimus-eluting coronary stent (SES) during in vitro elution were studied by correlated confocal Raman and atomic force microscopy (CRM and AFM, respectively). Chemical surface and subsurface maps of the SES were generated in the same region of interest by CRM and were correlated with surface topography measured by AFM at different elution times. For the first time, a direct correlation between drug-rich regions and the coating morphology was made on a drug-eluting medical device, linking drug release with pore formation, pore throats, and pore networks.

Adhesion and cohesion in structures containing suspended microscopic polymeric films.

This paper presents a novel technique for the characterization of adhesion and cohesion in suspended micro-scale polymeric films. The technique involves push-out testing with probes that are fabricated using focused ion beam techniques. The underlying stresses associated with different probe tip sizes were computed using a finite element model.

Forced degradation studies of rapamycin: identification of autoxidation products.

The immunosuppressant drug rapamycin, also known as Sirolimus, underwent autoxidation under mild conditions to give numerous monomeric and oligomeric compounds, which were generally characterized by size-exclusion chromatography and NP-HPLC with UV and MS detection. Some of the more predominant products, epoxides and ketones, were isolated and identified. Two epoxides and 10S-epimer of rapamycin were described for the first time.

Mass balance in rapamycin autoxidation.

The immunosuppressant drug rapamycin is a complex polyene-containing natural product which undergoes autoxidation. The resulting product mixtures contained numerous monomeric and oligomeric compounds, which represented challenges for addressing mass balance in forced degradation studies and in analysis of aged developmental drug-eluting stents. A combination of SEC with ultraviolet and refractive index detection and RP-HPLC was used to account for drug loss and product formation.