Dissolution and bioavailability of lercanidipine-hydroxypropylmethyl cellulose nanoparticles with surfactant

The objective of this study was to develop lercanidipine-hydroxypropylmethyl cellulose (HPMC) nanoparticles with high oral bioavailability. The lercanidipine-HPMC nanoparticles with/without surfactants were manufactured using a supercritical antisolvent (SAS) process. Gelucire 44/14, poloxamer 407, and D-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) were evaluated as surfactants. Spherical lercanidipine-HPMC nanoparticles with a mean particle size less than 400 nm were successfully prepared using a SAS process. The dissolution and oral bioavailability of lercanidipine was significantly increased by addition of surfactants. Especially lercanidipine-HPMC nanoparticles with TPGS showed a 2.47-fold higher oral bioavailability than raw material. Furthermore, the dissolution efficiency was strongly correlated to the in vivo C-max and AUC(0 -> 24h). Therefore, the preparation of HPMC nanoparticles with TPGS using a SAS process is a highly effective formulation strategy for enhanced oral bioavailability of lercanidipine. (C) 2014 Elsevier B.V. All rights reserved.