Formulation and evaluation of nisoldipine loaded solid lipid nanoparticles and nanostructured lipid carriers: Application to transdermal delivery

Abstract

Background: Nisoldipine is an anti hypertensive drug. Nisoldipine exhibits poor oral bioavailability (5%) because of rapid metabolism in the gut and liver. To overcome hepatic first pass metabolism and to enhance bioavailability, lipid based drug delivery systems (Solid lipid nanoparticles (SLN) and nano structure lipid carriers (NLC)) can be exploited. Objectives: In this work, effort was made to prepare novel particulate carrier systems such as stable Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for transdermal delivery of Nisoldipine (NSP). For this investigation, Carbopol 934 used as gel forming agent for hydrogel preparation. Methods: Aqueous dispersions of lipid nanoparticles made from Dynasan 114, 116, 118 were prepared by hot homogenization technique followed by ultrasonication and then optimized formulations of SLN and NLCs were incorporated into the freshly prepared hydrogels. Prepared lipid nanoparticles were characterized for particle size, zeta potential, entrapment efficiency, stability and in-vitro release profile. Also percutaneous permeation of SLN and NLCs were investigated in rat abdominal skin. Results: Analyzing the particles size by photon correlation spectroscopy (PCS) using Malven zeta sizer, which shows that the SLN and NLCs were in the range of 130-330 nm at room temperature. For all the tested formulations (SLN and NLCs), the entrapment efficiency was 72-97%. In-vitro drug release studies were performed for 24 hr. In these two cases the percentage drug release from gels enriched with SLN/NLC showed sustained release over period of 24 hr. In agreement with these results NSPNLC (Nisoldipine nanostructured lipid carriers) dispersion showed faster release. Formulation E4 showed faster release has less particle size and more zeta potential. Conclusion: Based on these, it was selected for further stability and ex-vivo studies. Both the SLN and NLC showed a sustained drug release over a period of 24 hr, but the sustained effect was more pronounced with the SLN and NLC gel formulations.