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. 2019 Mar 1:14:1587-1595.
doi: 10.2147/IJN.S195048. eCollection 2019.

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 Iqbal  2   3
Affiliations

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

Md Khalid Anwer et al. Int J Nanomedicine. .

Abstract

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: Poly(D,L-lactide-coglycolide); apremilast; bioavailability; nanoparticles; sustained release.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
FTIR spectra of APM and APM-loaded PLGA NPs (F1–F3). Abbreviations: APM, apremilast; PLGA NPs, poly(D,L-lactide-coglycolide) nano-particles.
Figure 2
Figure 2
DSC thermogram of APM and APM-loaded PLGA NPs (F1–F3). Abbreviations: APM, apremilast; DSC, differential scanning calorimetry; PLGA NPs, poly(D,L-lactide-coglycolide) nanoparticles.
Figure 3
Figure 3
Powder X-ray diffraction pattern of APM and APM-loaded PLGA NPs (F1–F3). Abbreviations: APM, apremilast; PLGA NPs, poly(D,L-lactide-coglycolide) nanoparticles.
Figure 4
Figure 4
SEM images of optimized APM-loaded PLGA NPs (F3). Abbreviations: APM, apremilast; PLGA NPs, poly(D,L-lactide-coglycolide) nanoparticles.
Figure 5
Figure 5
Release profile of pure APM and APM-loaded PLGA NPs (F3). Abbreviations: APM, apremilast; PLGA NPs, poly(D,L-lactide-coglycolide) nano-particles.
Figure 6
Figure 6
Higuchi release kinetics APM-loaded PLGA NPs (F3). Abbreviations: APM, apremilast; PLGA NPs, poly(D,L-lactide-coglycolide) nanoparticles.
Figure 7
Figure 7
Pharmacokinetic profile of pure APM suspension and APM-loaded PLGA NPs (F3). Abbreviations: APM, apremilast; PLGA NPs, poly(D,L-lactide-coglycolide) nanoparticles.
Figure 8
Figure 8
Representative MRM chromatogram of APM and IS in actual plasma sample at 1 hour after oral administration of APM (2 mg/kg). Abbreviations: APM, apremilast; IS, internal standard; MRM, multiple reaction monitoring.
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