Injection-molding versus extrusion as manufacturing technique for the preparation of biodegradable implants.

Polylactic acid (PLA) is a biocompatible and biodegradable material with wide utility for many applications, including the design of controlled-release systems for pharmaceutical agents. The factors determining the degradation kinetics of these systems include the composition and the molecular mass of the polymer, the morphology and the structure of the device, and the influence of thermal processes. The processing of the polymer determines the structure and design of the device, and influences to a high degree its morphology, namely its microporous structure, polymeric chain orientation and crystallinity.In this work, we aimed to compare the influence of two different implant manufacturing techniques, extrusion and injection-molding, on the in vitro degradation of the polymeric matrix. Both kinds of implants were loaded with a somatostatin analogue. Decrease in molecular weight, and polydispersity evolution during an accelerated in vitro degradation test were studied by size exclusion chromatography. Morphological changes in the polymeric matrix during degradation were followed after defined time intervals by means of scanning electron microscopy. Crystallinity studies were performed by differential scanning calorimetry and by X-ray analysis. Peptide stability in the polymeric matrix after both manufacturing methods was evaluated. Peptide release profiles, obtained in vitro during a week dissolution test, from both implant samples, were studied. It was shown that both molecular weight and polydispersity decreased after extrusion or injection-molding. This decrease was more pronounced with the latter technique. Crystallinity studies demonstrated that the crystalline network was not destroyed after both manufacturing methods. Peptide release profiles obtained in vitro were in good accordance with scanning electron microscopy. It was found that both manufacturing techniques had to be considered, although the extruded implants degraded more rapidly in vitro than the injection-molded ones.

Stability studies of a somatostatin analogue in biodegradable implants.

In recent years, peptides and proteins have received much attention as drug candidates. For many polypeptides, particularly hormones, it is desirable to release the drug continuously at a controlled rate over a period of weeks or even months, and thus a controlled release system is needed. Polylactic acid (PLA) is a biocompatible and biodegradable material with wide utility for many applications, including the design of controlled release systems for pharmaceutical agents. Pharmaceutical development of these delivery systems presents new problems in the area of stability assessment, especially for peptide drugs. In this study, we aimed to investigate the influence of different steps, during the manufacturing of an implant, on peptide stability in the polymeric matrix. Polylactic acid implants containing vapreotide, a somatostatin analogue, were prepared by extrusion. The effects of time, extrusion and temperature on the peptide stability were studied. The influence of various gamma sterilization doses, as well as the conditions under which the implants were irradiated, were also investigated. Peptide stability in the polymeric matrix was evaluated at various temperatures and at various time intervals up to 9 months.