Drug Design, Development and Therapy (May 2022)

Preparation, in vitro and in vivo Evaluation of Thermosensitive in situ Gel Loaded with Ibuprofen-Solid Lipid Nanoparticles for Rectal Delivery

  • Huang CH,
  • Hu PY,
  • Wu QY,
  • Xia MY,
  • Zhang WL,
  • Lei ZQ,
  • Li DX,
  • Zhang GS,
  • Feng JF

Journal volume & issue
Vol. Volume 16
pp. 1407 – 1431

Abstract

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Chun-hui Huang,1,2,* Peng-yi Hu,2,3,* Qiu-yan Wu,2,3 Ming-yan Xia,2,3 Wen-liu Zhang,3 Zhi-qiang Lei,3 Dong-xun Li,3 Guo-song Zhang,2,3 Jian-fang Feng1,2 1School of Pharmacy, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530200, People’s Republic of China; 2National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Nanchang, 330006, People’s Republic of China; 3Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guo-song Zhang, National Engineering Research Center of Chinese Medicine Solid Preparation Manufacturing Technology, Nanchang, 330006, People’s Republic of China, Email [email protected] Jian-fang Feng, School of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530200, People’s Republic of China, Email [email protected]: Ibuprofen (IBU), a nonsteroidal anti-inflammatory drug, shows poor gastrointestinal absorption due to its low solubility, which limits its clinical application.Objective: In the present study, we aimed to develop thermosensitive gel-mediated ibuprofen-solid lipid nanoparticles (IBU-SLN-ISG) to improve the dissolution and bioavailability of IBU after rectal delivery.Methods: IBU-loaded SLNs (IBU-SLNs) were developed and optimized applying Box-Behnken design. The optimized IBU-SLNs were characterized by physicochemical parameters and morphology. Then, the optimized IBU-SLNs was incorporated into the gel and characterized for gel properties and rheology and investigated its release in vitro, pharmacokinetics in vivo, rectal irritation and rectal retention time.Results: The optimized SLNs had an EE of 90.74 ± 1.40%, DL of 11.36 ± 1.20%, MPS of 166.77 ± 2.26 nm, PDI of 0.27 ± 0.08, and ZP of − 21.00 ± 0.59 mV. The FTIR spectra confirmed successful encapsulation of the drug inside the nanoparticle as only peaks responsible for the lipid could be identified. This corroborated well with XRD spectra, which showed a completely amorphous state of the IBU-SLNs as compared to the crystalline nature of the pure drug. The gelation temperature of the prepared IBU-SLN-ISG was 33.30 ± 0.78°C, the gelation time was 14.67 ± 2.52 s, the gel strength was 54.00 ± 1.41 s, and the mucoadhesion was (11.54± 0.37) × 102dyne/cm2. The in vitro results of IBU-SLNs and IBU-SLN-ISG showed a biphasic release pattern with initial burst release followed by sustained release. More importantly, IBU-SLN-ISG produced much better absorption of IBU and improved bioavailability in rats. In addition, IBU-SLN-ISG caused no irritation or damage to rectal tissues, and could be retained in the rectum for a long time.Conclusion: Thermosensitive in situ gel loaded with IBU-solid lipid nanoparticles might be further developed as a more convenient and effective rectal dosage form.Keywords: thermosensitive gel, ibuprofen, solid lipid nanoparticle, rectal delivery, bioavailability

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