College of Pharmacy, Freie Universität Berlin, Kelchstrasse 31, 12169, Berlin, Germany.
Pharm Res. 2010 Feb;27(2):371-9. doi: 10.1007/s11095-009-0033-x. Epub 2009 Dec 23.
To assess the feasibility of hot-melt extrusion (HME) for preparing implants based on protein/poly(lactide-co-glycolide) (PLGA) formulations with special emphasis on protein stability, burst release and release completeness.
Model protein (lysozyme)-loaded PLGA implants were prepared with a screw extruder and a self-built syringe-die device as a rapid screening tool for HME formulation optimization. Lysozyme stability was determined using DSC, FTIR, HPLC and biological activity. The simultaneous effect of lysozyme and PEG loadings was investigated to obtain optimized formulations with high drug loading but low initial release.
Lysozyme was recovered from implants with full biological activity after HME. The release from all implants reached the 100% value in 60-80 days with nearly complete enzymatic activity of the last fraction of released lysozyme. Pure PLGA implants with up to 20% lysozyme loading could be formulated without initial burst. The incorporation of PEG 400 reduced the initial burst at drug loadings in excess of 20%.
A complete lysozyme recovery in active form with a burst-free and complete release from PLGA implants prepared by hot-melt extrusion was obtained. This is in contrast to many reported microparticulate lysozyme-PLGA systems and suggests the great potential of hot-melt extrusion for the preparation of protein-PLGA implants.
评估热熔挤出（HME）用于制备基于蛋白质/聚（乳酸-共-乙醇酸）（PLGA）制剂的植入物的可行性，特别强调蛋白质稳定性、突释和释放完全性。
使用螺杆挤出机和自行设计的注射器模具装置制备模型蛋白（溶菌酶）载 PLGA 植入物，作为 HME 制剂优化的快速筛选工具。使用 DSC、FTIR、HPLC 和生物活性测定来确定溶菌酶的稳定性。研究溶菌酶和 PEG 载量的同时影响，以获得具有高载药量但低初始释放的优化制剂。
HME 后从植入物中回收了具有完整生物活性的溶菌酶。所有植入物的释放在 60-80 天内达到 100%值，最后释放的溶菌酶的最后一部分几乎完全具有酶活性。可以配制高达 20%载药量的纯 PLGA 植入物而没有初始突释。PEG 400 的掺入可减少超过 20%载药量时的初始突释。
通过热熔挤出制备的 PLGA 植入物中获得了完整的溶菌酶以活性形式回收，且无突释且完全释放。这与许多报道的微粒体溶菌酶-PLGA 系统形成对比，表明热熔挤出在制备蛋白质-PLGA 植入物方面具有巨大潜力。
