Preparation and optimization of media using Pluronic® micelles for solubilization of sirolimus and release from the drug eluting stents

Understanding the in-vitro release profile of drugs from drug eluting devices such as cardiac stent is crucial in designing and optimizing the drug embedded matrices. Sirolimus (SRL), a widely used anti-inflammatory/antiproliferative/immunosuppressive hydrophobic drug undergoes irreversible changes such as hydrolysis leading to erroneous assessment of the release profile. The release profile mainly depends on the drug release medium. The present study aims to develop and optimize the aqueous medium for the solubilization of SRL and in-vitro release method from drug eluting stent (DES). In the first stage of study several release media containing different buffer compositions, pH, and a series of micelle forming PEO–PPO–PEO block copolymers (known as Pluronic®) were examined for solubility and stability of SRL by reversed phase high performance liquid chromatography (RP-HPLC). SRL showed good solubility and stability at pH 4.0 (both in acetate buffer as well in phosphate buffer) in the presence of block copolymers. Solubilization of SRL was remarkably higher in P103 and P123 micelles than more hydrophilic F68 and F127. To get further insight into the underlying drug dissolution mechanisms, critical micellization temperature (CMT), and hydrodynamic size of micelles with and without drug incorporation were determined by UV–visible spectroscopy and dynamic light scattering (DLS) respectively. The micelle–water partition coefficient (P) and location of solubilized drug were also evaluated from a thermodynamics viewpoint. Finally, the optimized media were examined for the release of SRL from drug eluting stent; the data suggest that a release medium consisting of 0.1% P123 in phosphate buffer pH 4.0 is most suitable for evaluation of in-vitro release of SRL from DES.