Injectable Sustained-Release Depots of PLGA Microspheres for Insoluble Drugs Prepared by hot-Melt Extrusion.
PURPOSE
Progesterone (PRG) was selected as a model drug to develop a long-acting injection system for poorly water-soluble drugs.


METHODS
Microspheres with high density-low porosity were prepared by hot-melt extrusion (HME) combined with wet-milling as the representative formulation, and a microcrystal suspension was also studied as a comparison. The morphology, particle size and distribution, polymorphism, drug distribution, density and porosity were characterized by scanning electron microscopy, laser diffraction particle size analyzer, power X-ray diffraction and DSC respectively. The in vivo performance of the different formulations within 7 days after intramuscular injection was evaluated in male SD rats.


RESULTS
The drug-loading rate of the microspheres could be as high as 40%. The average initial burst release of the microspheres (PLGA lactide:glycolide = 75:25) was only 6.7% much lower than that of the microsuspension (25.7%) and a sustained release was exhibited for at least 7 days. The release mechanism was speculated to be as follows. The microspheres are a drug depot with drug microcrystals in the PLGA matrix which is a layer by layer honeycomb structure.


CONCLUSIONS
Microspheres prepared by HME combined with wet-milling could achieve a long-term sustained release effect as a novel long-acting formulation strategy.
['Guo|Yuting|Y|', 'Yang|Yunning|Y|', 'He|Luying|L|', 'Sun|Rong|R|', 'Pu|Chenguang|C|', 'Xie|Bin|B|', 'He|Haibing|H|', 'Zhang|Yu|Y|', 'Yin|Tian|T|', 'Wang|Yanjiao|Y|', 'Tang|Xing|X|']
D000818:Animals D002626:Chemistry, Pharmaceutical D003692:Delayed-Action Preparations D004337:Drug Carriers D065546:Drug Liberation D006801:Humans D019344:Lactic Acid D008297:Male D008863:Microspheres D010316:Particle Size D011100:Polyglycolic Acid D000077182:Polylactic Acid-Polyglycolic Acid Copolymer D016062:Porosity D011374:Progesterone D051381:Rats D017207:Rats, Sprague-Dawley D012995:Solubility D013499:Surface Properties
PLGA microsphere progesterone HME in vivo