Nanoparticles of Lovastatin: Design, Optimization and in vivo Evaluation

Int J Nanomedicine. 2020 Jun 17:15:4225-4236. doi: 10.2147/IJN.S241120. eCollection 2020.

Abstract

Introduction: The aim of the study was to optimize the processing factors of precipitation-ultrasonication technique to prepare nano-sized particles of Lovastatin (LA) for enhancing its solubility, dissolution rate and in vivo bioavailability.

Methods: LA nanoparticles (LANs) were prepared using precipitation-ultrasonication technique under different processing factors. LANs were characterized in terms of particle size, zeta potential and in vitro release. Stability studies at 4°C, 25°C and 40°C were conducted for optimum formulation. In addition, the in vivo bioavailability of the optimum formula was studied in comparison to a marketed product in white master rats.

Results: The optimized LAN formula (LAN15) had particle size (190±15), polydispersity index (0.626±0.11) and a zeta potential (-25±1.9 mV). The dissolution study of the nanosuspensions showed significant enhancement compared with pure drug. After 50 min, only 20.12±1.85% of LA was dissolved while 99.1±1.09% of LA was released from LAN15. Stability studies verified that nanosuspensions at 4°C and 25°C showed higher stability with no particle growth compared to the samples studied at 40°C. In vivo studies conducted in rats verified that there was 1.45-fold enhancement of Cmax of LAN15 as compared to marketed tablets.

Conclusion: Nanoparticle prepared by ultrasonication-assisted precipitation method is a promising formula for enhancing the solubility and hence the bioavailability of Lovastatin.

Keywords: HPMC; antisolvent; bioavailability; factors; hyperlipidemia; nano size.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Calorimetry, Differential Scanning
  • Lovastatin / blood
  • Lovastatin / chemistry
  • Lovastatin / pharmacokinetics
  • Lovastatin / pharmacology*
  • Male
  • Nanoparticles / chemistry*
  • Particle Size
  • Rats, Wistar
  • Solubility
  • Spectroscopy, Fourier Transform Infrared
  • Static Electricity
  • Suspensions

Substances

  • Suspensions
  • Lovastatin