In Vitro-In Vivo Relationship of Amorphous Insoluble API (Progesterone) in PLGA Microspheres
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The mechanism of PRG release from PLGA microspheres was studied and the correlation of in vitro and in vivo analyses was assessed.
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.
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.
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 WORDSamorphous crystal depot IVIVC PLGA microspheres release mechanism
Active pharmaceutical ingredient
In vitro and in vivo correlation
Liquid chromatography–mass spectrometry/mass spectrometry
Powder x-ray diffraction
Sprague – Dawley
Sodium dodecyl sulfate
Scanning electron microscopy
Glass transition temperature
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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