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Pharmaceutical Research

, Volume 34, Issue 12, pp 2787–2797 | Cite as

In Vitro-In Vivo Relationship of Amorphous Insoluble API (Progesterone) in PLGA Microspheres

  • Chenguang Pu
  • Qiao Wang
  • Hongjuan Zhang
  • Jingxin Gou
  • Yuting Guo
  • Xinyi Tan
  • Bin Xie
  • Na Yin
  • Haibing He
  • Yu Zhang
  • Yanjiao WangEmail author
  • Tian YinEmail author
  • Xing Tang
Research Paper

Abstract

Purpose

The mechanism of PRG release from PLGA microspheres was studied and the correlation of in vitro and in vivo analyses was assessed.

Methods

PRG-loaded microspheres were prepared by the emulsion-evaporate method. The physical state of PRG and microstructure changings during the drug release period were evaluated by powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) respectively. Pharmacokinetic studies were performed in male Sprague-Dawley rats, and the in vivo-in vitro correlation (IVIVC) was established by linear fitting of the cumulative release (%) in vitro and fraction of absorption (%) in vivo.

Results

PXRD results indicated recrystallization of PRG during release. The changes of microstructure of PRG-loaded microspheres during the release period could be observed in SEM micrographs. Pharmacokinetics results performed low burst-release followed a steady-released manner. The IVIVC assessment exhibited a good correlation between vitro and in vivo.

Conclusions

The burst release phase was caused by diffusion of amorphous PRG near the surface, while the second release stage was impacted by PRG-dissolution from crystal depots formed in microspheres. The IVIVC assessment suggests that the in vitro test method used in this study could predict the real situation in vivo and is helpful to study the release mechanism in vivo.

KEY WORDS

amorphous crystal depot IVIVC PLGA microspheres release mechanism 

ABBREVIATIONS

API

Active pharmaceutical ingredient

DCM

Dichloromethane

f

Absorption fraction

i.m.

Intramuscular

IVIVC

In vitro and in vivo correlation

LC–MS/MS

Liquid chromatography–mass spectrometry/mass spectrometry

MS

Microsphere

Mw

Molecular weight

PGA

poly(glycolide)

PLA

poly(L-lactide)

PLGA

poly(D,L-lactide-co-glycolide)

PRG

Progesterone

PVA

Polyvinyl alcohol

PXRD

Powder x-ray diffraction

s.c.

Subcutaneous

SD

Sprague – Dawley

SDS

Sodium dodecyl sulfate

SEM

Scanning electron microscopy

SI

Saline injection

Tg

Glass transition temperature

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

The authors wish to thank Amanda Pearce for linguistic assistance. This work was supported by the National Natural Science Foundation of China No. 81673378.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Chenguang Pu
    • 1
  • Qiao Wang
    • 1
  • Hongjuan Zhang
    • 1
  • Jingxin Gou
    • 1
  • Yuting Guo
    • 1
  • Xinyi Tan
    • 1
  • Bin Xie
    • 1
  • Na Yin
    • 1
  • Haibing He
    • 1
  • Yu Zhang
    • 1
  • Yanjiao Wang
    • 1
    Email author
  • Tian Yin
    • 2
    Email author
  • Xing Tang
    • 1
  1. 1.School of PharmacyShenyang Pharmaceutical UniversityShenyangChina
  2. 2.School of Functional food and WineShenyang Pharmaceutical UniversityShenyangChina

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