Physicochemical characterization and pharmacokinetic evaluation of rosuvastatin calcium incorporated solid lipid nanoparticles

Al-Heibshy F. N. S., BAŞARAN E., ARSLAN R., ÖZTÜRK N., EROL K., DEMİREL M.

INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol.578, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 578
  • Publication Date: 2020
  • Doi Number: 10.1016/j.ijpharm.2020.119106
  • Journal Name: INTERNATIONAL JOURNAL OF PHARMACEUTICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Keywords: Rosuvastatin calcium, Solid lipid nanoparticles (SLNs), Oral bioavailability, CONTROLLED DRUG-DELIVERY, CACO-2 CELL MONOLAYERS, IN-VITRO PERMEABILITY, ORAL BIOAVAILABILITY, SLN, FORMULATION, CYCLOSPORINE, STABILITY, RELEASE, PHARMACOLOGY
  • Anadolu University Affiliated: Yes

Abstract

Rosuvastatin calcium (RCa) is a very efficient antihyperlipidemic agent, however, being a BCS class II drug, results in poor oral bioavailability. The present study focused on the enhancement of oral bioavailability of RCa with solid lipid nanoparticles (SLNs). Physicochemical properties of the particles were evaluated by particle size (PS), polidispersity index (PDI), zeta potential (ZP), DSC, FT-IR, XRD, (HNMR)-H-1 analyses. Entrapment efficiency (EE), drug loading capacity (DL), in vitro release and release kinetics were also analyzed. Safety and efficacy of the formulations were analyzed by cytotoxicity, permeability and pharmacokinetic studies. PS values were ranged between similar to 134 and 351 nm with homogenous size distribution (PDI similar to 0.130-0.33) and ZP data were valued within the range of similar to -17 mV to - 41 mV. The SLN2 formulation showed the best cytotoxicity test results and had medium permeability (P-app 5.72 x 10(-6) cm sec(-1) ) while pure RCa resulted in low permeability (P-app 3.08 x 10(-7) cm sec(-1)). According to the stability analyses (3 months) 5 +/- 3 degrees C and 25 +/- 2 degrees C were found suitable storage temperatures for SLNs. Pharmacokinetic studies confirmed significant improvement in C-max (1.4 fold) and AUC(last )(8.5 fold) by SLNs in comparison with the pure drug indicating the enhanced biopharmaceutical performance of the RCa loaded SLNs.