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AAPS PharmSciTech

, Volume 19, Issue 5, pp 2301–2310 | Cite as

Preparation and Pharmacokinetics Evaluation of Solid Self-Microemulsifying Drug Delivery System (S-SMEDDS) of Osthole

  • Chaojie Sun
  • Yun Gui
  • Rongfeng Hu
  • Jiayi Chen
  • Bin Wang
  • Yuxing Guo
  • Wenjie Lu
  • Xiangjiang Nie
  • Qiang Shen
  • Song Gao
  • Wenyou Fang
Research Article
  • 62 Downloads

Abstract

The study was performed aiming to enhance the solubility and oral bioavailability of poorly water-soluble drug osthole by formulating solid self-microemulsifying drug delivery system (S-SMEDDS) via spherical crystallization technique. Firstly, the liquid self-microemulsifying drug delivery system (L-SMEDDS) of osthole was formulated with castor oil, Cremophor RH40, and 1,2-propylene glycol after screening various lipids and emulsifiers. The type and amount of polymeric materials, good solvents, bridging agents, and poor solvents in S-SMEDDS formulations were further determined by single-factor study. The optimal formulation contained 1:2 of ethyl cellulose (EC) and Eudragit S100, which served as matrix forming and enteric coating polymers respectively. Anhydrous ethanol and dichloromethane with a ratio of 5:3 are required to perform as good solvent and bridging agent, respectively, with the addition of 0.08% SDS aqueous solution as poor solvent. The optimized osthole S-SMEDDS had a high yield (83.91 ± 3.31%) and encapsulation efficiency (78.39 ± 2.25%). Secondly, osthole L-SMEDDS was solidified to osthole S-SMEDDS with no significant changes in terms of morphology, particle size, and zeta potential. In vitro release study demonstrated a sustained release of the drug from osthole S-SMEDDS. Moreover, in vivo pharmacokinetic study showed that the Tmax and mean residence time (MRT(0-t)) of osthole were significantly prolonged and further confirmed that osthole S-SMEDDS exhibited sustained release effect in rabbits. Comparing with osthole aqueous suspension and L-SMEDDS, osthole S-SMEDDS increased bioavailability by 205 and 152%, respectively. The results suggested that S-SMEDDS was an effective oral solid dosage form, which can improve the solubility and oral bioavailability of poorly water-soluble drug osthole.

KEY WORDS

osthole self-microemulsion spherical crystallization technique bioavailability 

Notes

Acknowledgements

We thank Dr. Jun Shao of St. John’s University for his support in the design and writing of the thesis.

Funding Information

This project was supported by the National Natural Science Foundation of China (no. 81274100, no. 81573615) and Project of Scientific Research Fund of Anhui University of Chinese Medicine (no. 2016zr009).

Compliance with Ethical Standards

The animal experiments were approved and supervised by the Animal Experimental Ethical Committee of Anhui Medical University (Hefei, China).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Chaojie Sun
    • 1
  • Yun Gui
    • 1
  • Rongfeng Hu
    • 1
    • 2
  • Jiayi Chen
    • 3
  • Bin Wang
    • 1
  • Yuxing Guo
    • 3
  • Wenjie Lu
    • 4
  • Xiangjiang Nie
    • 1
  • Qiang Shen
    • 1
  • Song Gao
    • 1
  • Wenyou Fang
    • 1
  1. 1.Key Laboratory of Xin’an Medicine, Ministry of Education, Anhui Province, Key Laboratory of R&D of Chinese MedicineAnhui University of Traditional Chinese MedicineHefeiPeople’s Republic of China
  2. 2.Anhui “115” Xin’an Medicine Research & Development Innovation TeamHefeiPeople’s Republic of China
  3. 3.Department of Pharmaceutical Sciences, College of pharmacy and Health SciencesSt. John’s UniversityJamaicaUSA
  4. 4.School of PharmacyChina Pharmaceutical UniversityNanjingPeople’s Republic of China

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