Polymer blends used to develop felodipine-loaded hollow microspheres for improved oral bioavailability

Abstract

Felodipine (FD) has been widely used in anti-hypertensive treatment. However, it has extremely low aqueous solubility and poor bioavailability. To address these problems, FD hollow microspheres as multiple-unit dosage forms were synthesized by a solvent diffusion evaporation method. Particle size of the hollow microspheres, types of ethylcellulose (EC), amounts of EC, polyvinyl pyrrolidone (PVP) and FD were investigated based on an orthogonal experiment of three factors and three levels. In addition, the release kinetics in vitro and pharmacokinetics in beagle dogs of the optimized FD hollow microspheres was investigated and compared with Plendil (commercial FD sustained-release tablets) as a single-unit dosage form. Results showed that the optimal formulation was composed of EC10 cp:PVP:FD (0.9:0.16:0.36, w/w). The FD hollow microspheres were globular with a hollow structure and have high drug loading (17.69±0.44%) and floating rate (93.82±4.05%) in simulated human gastric fluid after 24h. Pharmacokinetic data showed that FD hollow microspheres exhibited sustained-release behavior and significantly improved relative bioavailability of FD compared with the control. Pharmacodynamic study showed that the FD hollow microspheres could effectively lower blood pressure. Therefore, these findings demonstrated that the hollow microspheres were an effective sustained-release delivery system for FD.