Improved lysozyme stability and release properties of poly(lactide-co-glycolide) implants prepared by hot-melt extrusion.
OBJECTIVE
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.


METHODS
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.


RESULTS
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%.


CONCLUSIONS
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.
Ghalanbor
Zahra
Z
College of Pharmacy, Freie Universität Berlin, Kelchstrasse 31, 12169, Berlin, Germany.
Körber
Martin
M
Bodmeier
Roland
R
D020341:Absorbable Implants; D003692:Delayed-Action Preparations / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D004795:Enzyme Stability; D006358:Hot Temperature; D019344:Lactic Acid / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D009113:Muramidase / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011100:Polyglycolic Acid / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D003692:Delayed-Action Preparations; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D009113:Muramidase