Biodegradable microparticles for sustained release of a new GnRH antagonist - part I: Screening commercial PLGA and formulation technologies

Article Article scientifique Article Biodegradable microparticles for sustained release of a new GnRH antagonist - part I: Screening commercial PLGA and formulation technologies eng 2003 author Schwach Grégoire 512594 author Oudry Nathalie 116037 author Delhomme Sophie 522699 author Lück Martin author Lindner Hans author Gurny Robert 24779 327-336 10.1016/s0939-6411(03)00096-1 14602174 0939-6411 The formulation of a new GnRH antagonist (degarelix) in biodegradable poly(DL-lactide-co-glycolide) (PLGA) microparticles was investigated for the development of a 3-month sustained release formulation to treat prostate cancer. The aim was to screen formulation technologies and distinct copolymers to produce microparticles (MP) of different types with good entrapment efficiency (>85%) and peptide purity (>95%) after gamma sterilization. Basically, three types of degarelix-loaded MP (4, 8 and 16% w/w nominal content) were produced with solvent and non-solvent technologies, namely double-emulsion solvent evaporation, spray-drying and two extrusion methods. Besides composition, commercial copolymers differing in residual monomer content and functional group at the carboxylic terminus (acid or ester) were characterized and employed. Peptide loading capacity and purity, as well as shape, size characteristics, and porosity of the produced microparticles were discussed in relation to technology and copolymer choice. Spray-drying and micro-extrusion were the two preferred formulation technologies because of higher entrapment efficiency and better preservation of peptide purity during production and gamma-sterilization. The impact of formulation technologies on the MP characteristics overwhelmed the impact of copolymer selection. Nevertheless, one particular polymer was discarded since it was more susceptible towards radiolytic degradation. The resulting degarelix-MP will be tested in a biological assay for selection of the formulation based on performance. Peptide drug delivery GnRH antagonist Degarelix Poly(lactic acid) Poly(lactic acid) copolymers Microparticle Microsphere Extrusion Prostate cancer Dewey 615 31 Section des sciences pharmaceutiques 17 false European journal of pharmaceutics and biopharmaceutics 56 3 0f3fa5d4-07af-4429-94ab-2f65b881355f Article (Published version) Restricted G.Schwach.pdf 401839 application/pdf restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Biodegradable microparticles for sustained release of a new GnRH antagonist - part I: Screening commercial PLGA and formulation technologies	European journal of pharmaceutics and biopharmaceutics			2003	472	1

Archive ouverte UNIGE

Delhomme, Sophie