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AAPS PharmSciTech

, Volume 19, Issue 3, pp 1254–1263 | Cite as

Preparation and Evaluation of Progesterone Nanocrystals to Decrease Muscle Irritation and Improve Bioavailability

  • Li Li
  • Wanqing Li
  • Jianxu Sun
  • Hui Zhang
  • Jing Gao
  • Fei Guo
  • Xi Yang
  • Xun Zhang
  • Ying Li
  • Aiping Zheng
Research Article

Abstract

Progesterone (PG) is a crucial immunomodulatory agent during early pregnancy, and nowadays PG oil-based injection (PG/OI) has a huge market all over the world. However, PG/OI may accumulate the local muscle and further cause irritations after long-term administration. In this study, PG nanocrystals (PG/NCs) injection was developed to decrease muscle toxicity. PG/NCs injection containing 10% (w/v) PG was first prepared using a wet grinding method. Then, particle size, zeta potential, morphology powder, X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) studies were carried out to evaluate the characteristics of dosage form. The rabbit muscle irritation, hemolysis, and rat pharmacokinetics tests were used to estimate the in vivo characteristics of PG/NCs. The results showed that the mean particle size and the zeta potentials of NCs were 299.5 ± 9.0 nm and − 36.8 ± 1.5 mV, respectively. The crystalline state of PG/NCs was not altered during particle size reduction according to PXRD, DSC, and FTIR results. Muscle irritation presented that PG/NCs had lower irritation than that of PG/OI. Hemolysis test suggested that PG/NCs injection was functioned without hemolysis and red cell agglutination. The pharmacokinetics study showed that the AUC0t and Cmax of PG/NCs was 3.2-fold (p < 0.05) and 3.1-fold higher than PG/OI, which demonstrated that PG/NCs injection had greater bioavailability than PG/OI. Therefore, it was obvious that PG/NCs injection exhibited a lower muscle irritation, hemolysis rate, and higher bioavailability, which was a better dosage form than OI.

KEY WORDS

progesterone nanocrystals injection muscle irritation rat pharmacokinetics LC-MS/MS carotid intubation rat model 

Abbreviations

PG

progesterone

PG/NCs

PG nanocrystals

PG/OI

PG oil-based injection

Notes

Funding Information

This work was supported by the Natural Science Foundation of China (grant numbers 81573357) and the Beijing Natural Science Foundation (grant numbers 7162148).

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflicts of interest.

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Li Li
    • 1
  • Wanqing Li
    • 2
  • Jianxu Sun
    • 1
  • Hui Zhang
    • 1
  • Jing Gao
    • 1
  • Fei Guo
    • 1
  • Xi Yang
    • 1
  • Xun Zhang
    • 1
  • Ying Li
    • 1
  • Aiping Zheng
    • 1
  1. 1.State Key Laboratory of Toxicology and Medical CountermeasuresBeijing Institute of Pharmacology and ToxicologyBeijingChina
  2. 2.School of Preclinical MedicineBeijing University of Chinese MedicineBeijingChina

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