Preparation of sustained release apremilast-loaded PLGA nanoparticles: in vitro characterization and in vivo pharmacokinetic study in rats

Background: Apremilast (APM) is a novel, orally administered small molecule drug approved for treatment of psoriasis or psoriatic arthritis. Due to its low solubility and permeability, it is classified as a class IV drug according to BCS classification. Dose titration is recommended during APM treatment due to its tolerability and twice-daily dosing regimen issues. Materials and Methods: In this study, three different APM-loaded PLGA nanoparticles (F1-F3) were prepared by single emulsion and evaporation method. Based on particle size, PDI, zeta potential (ZP), entrapment efficiency (% EE), drug loading (% DL), and spectral characterization, the nanoparticles (F3) were optimized. The F3 nanoparticles were further evaluated for in vitro release and in vivo pharmacokinetic studies in rats. Results: The optimized nanoparticles (F3) had particles size 307.3 +/- 8.5 nm with a low PDI value 0.317, ZP of -43.4 +/- 2.6 mV, EE of 61.1 +/- 1.9% and DL of 1.9 +/- 0.1%. The in vitro release profile showed a sustained release pattern of F3 nanoparticles of APM. The pharmacokinetic results showed 2.25 times increase in bio-availability of F3 nanoparticles compared to normal APM suspension. Moreover, significant increase in half-life and mean residence time confirms long-term retention of F3 nanoparticles. Conclusion: Bioavailability enhancement along-with long-term retention of the APM-loaded PLGA nanoparticles might be helpful for the once-daily regimen treatment.