Drug Delivery and Translational Research

, Volume 9, Issue 1, pp 344–356 | Cite as

Effect of supersaturation on the oral bioavailability of paclitaxel/polymer amorphous solid dispersion

  • Linlin Miao
  • Yuheng Liang
  • Wenli Pan
  • Jingxin Gou
  • Tian Yin
  • Yu Zhang
  • Haibing He
  • Xing TangEmail author
Original Article


The aim of the present investigation was to evaluate the effect of supersaturation on the oral absorption of paclitaxel (PTX) in vivo. To achieve this, a PTX amorphous solid dispersion (ASD) was prepared by the solvent cast method. Among the enteric polymers tested, hypromellose acetate succinate (HPMCAS) MF was found to be the most suitable polymer for maintaining PTX supersaturation and inhibiting crystallization in vitro. The dissolution rate and extent of the ASD was remarkably improved compared with a physical mixture (PM) of PTX, HPMCAS-MF, and Poloxamer 188 (F68), reaching an apparent drug concentration of 25–30 μg/mL and maintaining it for more than 2 h. The liquid–liquid phase separation (LLPS) concentration of PTX in the presence of HPMCAS-MF was determined to be 23 μg/mL, which was different to that of 40 μg/mL in the absence of polymer. It indicated that HPMCAS was substantially incorporated into the drug-rich phase. Also, HPMCAS could absorb to the PTX surface and provided an interfacial barrier for crystal growth, as well as retard the incorporation of PTX from solution into the growing crystal lattice. The results of X-ray diffraction, differential scanning calorimetry analysis, and transmission electron microscopy confirmed that PTX existed in the amorphous state in the solid dispersion. Compared with the PM group, the ASD prepared with HPMCAS-MF and F68 achieved a 1.78-fold increase in relative oral bioavailability, while PTX solution yielded a 1.56-fold increase, which could be explained that the solubility and the permeability of PTX were not increased simultaneously through supersaturation in vivo. Likely, it was because Cremophor inhibited P-glycoprotein in the intestine to some extent and maintained PTX at a higher concentration for a longer time.


Supersaturation Bioavailability Amorphous solid dispersion Polymer PTX 


Funding information

This work was supported by the National Basic Research Program of China (973 Program, No. 2015CB932103), National Natural Science Foundation of China (No. 81673378), and China Postdoctoral Science Foundation (2016M600216).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All institutional and national guidelines for the care and use of laboratory animals were followed.


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Copyright information

© Controlled Release Society 2018

Authors and Affiliations

  1. 1.Department of Pharmaceutics, School of PharmacyShenyang Pharmaceutical UniversityShenyangChina
  2. 2.School of Functional Food and WineShenyang Pharmaceutical UniversityShenyangChina

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