Hans Lindner

Polymer erosion in PLGA microparticles produced by phase separation method.

This article deals with polymer erosion in biodegradable microparticles produced using the phase separation method. Poly(lactic-co-glycolic acid) copolymers with different compositions and molecular weights were employed. The microparticles were stored in phosphate buffer for 6 months. The molecular weight of the polymers was determined by size exclusion chromatography, and the weight loss was monitored gravimetrically. No weight loss was measured in the first weeks, although the molecular weight decreased significantly already from the start. After a certain storage period which was found to be specific for the type of polymer, the weight of the microparticles decreased rapidly. The start of this weight loss occurred when the molecular weight of the polymer in the degrading microparticles reached a threshold of approximately 15,000. This critical molecular weight was found to be identical for all investigated polymers, i.e. it was independent of the initial molecular weight of the polymer and of the lactic-glycolic ratio.

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

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.

Comparison between a twin-screw extruder and a rotary ring die press. I. Influence of formulation variables

Pellets were produced on two different types of extruders: a twin-screw extruder and a rotary ring die press. The solubility and the particle size of the excipients were used as formulation variables. All formulations were processed with different moisture content. The power consumption during extrusion, pellet shape and size were selected as yield values. For each formulation and process an optimal moisture content of the extrudate could be determined which resulted in spherical pellets without agglomeration tendency. The optimal moisture content was influenced by both the type of extruder and the selected formulation variables. The optimal moisture content was higher using the twin-screw extruder compared to the ring die press which was explained by the crystallite-gel model. With increasing solubility of the excipient the optimal moisture content was shifted towards lower values. With the ring die press an additional influence of the particle size could be observed: a lower particle size increased the optimal moisture content. The particle size of round pellets depended on the moisture content of the extrudate: due to shrinking during drying extrudates with a high moisture content resulted in the lowest particle size independent of the studied influence variables.