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Construction and evaluation of a phospholipid-based phase transition in situ gel system for brexpiprazole

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Abstract

The objective of this study was to develop phospholipid-based injectable phase transition in situ gels (PTIGs) for the sustained release of Brexpiprazole (Brex). Phospholipid (Lipoid S100, S100) and stearic acid (SA) were used as the gel matrix which was dissolved in biocompatible solvent medium-chain triglyceride (MCT), N-methyl pyrrolidone (NMP), and ethanol to obtain PTIGs solution. The Brex PTIG showed a solution condition of low viscosity in vitro and was gelatinized in situ in vivo after subcutaneous injection. Both in vitro release assay and in vivo pharmacokinetics study in SD rats displayed that Brex in PTIGs could achieve a sustained release, compared with brexpiprazole solution (Brex-Sol) or brexpiprazole suspension (Brex-Sus). The Brex-PTIGs had good degradability and biocompatibility in vivo with rare inflammation at the injection site. Among the three Brex-PTIG formulations, Brex-PTIG-3 with the SA in the formulation had the greatest gelation viscosity, the lowest initial release rate, and the most stable release profile with sustained release of up to 60 days. The above results indicated that, as a novel drug delivery system, the Brex-PTIGs offered a new option for the clinical treatment of patients with schizophrenia.

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Data availability

The data presented in this study are available upon request.

Abbreviations

PTIGs:

phospholipid-based injectable phase transition in situ gels

NMP:

N-methyl pyrrolidone

S100:

soya bean phosphatidyl Choline

SA:

stearic acid

MCT:

medium chain triglyceride

Brex-Sol:

Brexpiparzole solution

Brex-Sus:

Brexpiparzole suspension

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Acknowledgments

The study leading to the reported results was funded by the Program of Postgraduate Joint Training Base of Chongqing (Chongqing Medical University& Yaopharma Co., Ltd joint training base for postgraduate in pharmacy) (to Huali Chen and Yan Zhang), and the Science and Technology Research Program of Chongqing Municipal Education Commission (grant no. KJQN202000407; to Huali Chen).

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Author notes

  1. Ran Tao and Li Liu are contributed equally to this paper.

Authors and Affiliations

  1. College of Pharmacy, Chongqing Medical University, Chongqing, 400042, China

    Ran Tao, Qianyu Zhang, Fang Ren, Lu Zhou, Baoyan Chen, Kexin Wu & Huali Chen

  2. Yaopharma Co, Ltd, No. 100, Xingguang Ave, Chongqing, 401121, China

    Li Liu, Yingxin Xiong, Xiangyu Lv, Linbo He & Yan Zhang

Authors
  1. Ran Tao
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Contributions

Ran Tao: Conceptualization, Methodology, Investigation, Data curation, Writing an original draft, Visualization. Li Liu: Methodology, Investigation, Data curation, Visualization, Supervision, Writing - review & editing. Yingxin Xiong: Methodology, Investigation, Resources, Supervision. Qianyu Zhang: Methodology, Investigation, Writing - review & editing. Xiangyu Lv: Data curation, Formal analysis. Linbo He: Data curation, Formal analysis, Resources. Fang Ren: Validation, Methodology. Lu Zhou: Methodology, Software. BaoYan Chen: Formal analysis, Software. Kexin Wu: Validation, Visualization. Yan Zhang: Project administration, Resources, Supervision. Huali Chen: Funding acquisition, Conceptualization, Supervision, Writing - review & editing.

Corresponding authors

Correspondence to Yan Zhang or Huali Chen.

Ethics declarations

Ethics approval

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of Chongqing Management Approach of Laboratory Animal (chongqing government order NO.195).

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Not applicable.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Tao, R., Liu, L., Xiong, Y. et al. Construction and evaluation of a phospholipid-based phase transition in situ gel system for brexpiprazole. Drug Deliv. and Transl. Res. 13, 2819–2833 (2023). https://doi.org/10.1007/s13346-023-01349-0

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