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

Md Khalid Anwer,1 Muqtader Mohammad,1 Essam Ezzeldin,2,3 Farhat Fatima,1 Ahmed Alalaiwe,1 Muzaffar Iqbal2,3 1Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia; 2Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; 3Bioavailability Laboratory, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia 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. Keywords: apremilast, Poly(D,L-lactide-coglycolide), nanoparticles, bioavailability, sustained releas