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Evaluation of microstructure, dissolution rate, and oral bioavailability of paclitaxel poloxamer 188 solid dispersion

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Abstract

Poor solubility is a major challenge for enhancing the oral bioavailability and clinical application of many drugs, including the broad-spectrum chemotherapy drug paclitaxel (PTX). A practical approach to improving the solubility of insoluble drugs is through the use of solid dispersion (SD). This study aimed to investigate the potential of the triblock copolymer, poloxamer 188 (P188), as a carrier for preparing solid dispersion of paclitaxel using spray drying technology. We systematically studied its microstructure, dissolution behavior in vitro, and pharmacokinetics. Our findings demonstrate that PTX exists in an amorphous state in copolymer composed of polyoxyethylene-polyoxypropylene-polyoxyethylene (PEO-PPO-PEO) P188, with stronger miscibility with hydrophobic PPO segments. All three in vitro dissolution models revealed that the release rate of drugs in SD was significantly higher compared to that of physical mixtures (PM) as well as raw drugs. Furthermore, our pharmacokinetic results showed that the area under the curve(AUC) of PTX in SD was 6 times higher than that of active pharmaceutical ingredient(API), 4.5 times higher than PM, and the highest blood drug concentration (Cmax) reached 357.51 ± 125.54 (ng/mL), approximately 20 times higher than API. Overall, our findings demonstrate that the dissolution rate of amorphous PTX in SD significantly improves, effectively enhancing the oral bioavailability of PTX.

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The datasets used or analyzed during the current study are available from the corresponding author upon reasonable request.

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Funding

This research was supported by the science and technology of Qinghai Province (No. 2022-QY-201) and the National Natural Science Foundation of China (Project No. 82060644).

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Authors and Affiliations

  1. Medical College, Qinghai University, Xining, 810001, Qinghai, People’s Republic of China

    Yao Liu, Yong Zhang, Qiuli Yan & Xueping Zhong

  2. State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, 810001, Qinghai, People’s Republic of China

    Chunhui Hu

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  1. Yao Liu
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Contributions

Conceptualization, experimental work, writing (draft), and writing revision: YL; experimental work and writing (draft): YZ; experimental work: QL.Y; and conceptualization and manuscript revision: XP.Z and CH.H.

Corresponding author

Correspondence to Chunhui Hu.

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All animal study protocols were approved by the Institutional Animal Care and Utilization Committee of Qinghai University, CAS (approval numbers -QHU -IPC -23041).

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Not applicable. No human studies have been performed in this research.

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The authors declare no competing interests.

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Liu, Y., Zhang, Y., Yan, Q. et al. Evaluation of microstructure, dissolution rate, and oral bioavailability of paclitaxel poloxamer 188 solid dispersion. Drug Deliv. and Transl. Res. 14, 329–341 (2024). https://doi.org/10.1007/s13346-023-01400-0

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