A Novel Micron-Size Particulate Formulation of Felodipine with Improved Release and Enhanced Oral Bioavailability Fabricated by Coaxial Electrospray

The antihypertensive drug felodipine (FD) is a typical biopharmaceutics classification system (BCS) II drug; thus, improving the dissolution rate of FD is very important to enhance its bioavailability. Besides, according to the in situ “close loop” perfusion assay, we found that the jejunum is the main absorptive site, then the duodenum and ileum. Consequently, a novel micron-size particulate of FD in a core-shell structure was fabricated by a coaxial electrospray technique; within the drug delivery system, Hypromellose K4M (HPMC K4M) was selected as a sheath material to prolong the retention time in the upper GI tract, while povidone K30 (PVP K30) was mixed with FD in the inner layer. The dissolution study in three different media (0.02% Tween-80 solution; phosphate buffer containing 0.02% Tween-80, pH 6.8; and HCl solution containing 0.02% Tween-80, pH 1.2) demonstrated that FD-loaded coaxial electrospray particles (F-COES) could greatly improve the dissolution of FD. Furthermore, in vivo pharmacokinetics revealed that F-COES emerged no changes in the half-life but significantly prolonged the tmax and increased the oral bioavailability. Collectively, this work supplies a promising drug release system that will improve the dissolution and enhance the bioavailability simultaneously for those poorly water-soluble drugs mainly absorbed in the upper GI tract.