Dissertation (Metadaten)
Titel:Herstellung und Charakterisierung neuer Blockcopolymere auf Polylaktid- und Polyglykolid-Basis und ihr Einsatz zur Herstellung von Mikropartikeln
Autor:Günter Nykamp
Fakultät:Mathematisch-Naturwissenschaftliche Fakultät
DDC Sachgebiet:660 Technische Chemie
Datum der mdl. Prüfung:15.12.2004
Referent(in):Prof. Dr. Dr. B. W. Müller
Korreferent(en) Korreferentin:Dr. habil. G. Rafler
Beschreibung (original):Keine deutschsprachige Zusammenfassung vorhanden.
(übersetzt):The first objective of the present thesis was the modification of the physicochemical properties of commercially available polymers of the Poly(lactide-co-glycolide) type with statistical monomer distribution focusing on the glass-transition temperature. This target was reached by blocking the homopolymers Poly-D,L-lactide or Poly-L,L-lactide with Polyglycolide. The polymer syntheses were carried out by continuous reactive compounding processes using a twin-screw extruder. The synthesized blocked copolymers showed higher glass-transition temperatures and, therefore, improved storage performance compared to the commercially available copolymers at similar or even lower molecular weights and identical monomer composition. The degradation properties were not affected significantly. It was shown that, beside the monomeric composition and the molecular weight of the copolymers, the length of the Poly-D,L-lactide blocks affects the glass transition temperature strongly. The degradation patterns of the copolymers were investigated by combining several methods. It was shown that the blocklengths behave as expected. This means that first the glycolide part and then the lactide part was decomposed. The second aim of this study was the optimization of the microparticle preparation by using the melt-grinding technique. The investigations were carried out by statistical design plans. It could be observed that there are clear differences in the behaviour of crystalline and amorphous substances during the jet-milling step of the production process. Crystalline substances are comminuted to their final particle size during the first milling step whereas the particle size of amorphous substances is reduced stepwise within several grinding steps. Furthermore, it was observed that a sole size reduction of the polymeric poarticles is obtainable at much lower pressures than needed for particle surface smoothening. In this latter case, a higher milling intensity has to be applied by increasing the milling pressure and the number of milling cycles. Investigations of the release behaviour of estrioltriacetate loaded Poly-D,L(lactide-co-glycolide) microparticles revealed a square root release pattern without showing a burst-effect at all. To clarify the lack of burst effect, investigations of the physicochemical properties of the microparticles were carried out. The examination of the enthalpic relaxation behaviour revealed that the energy consumption by the polymer which was used during this process decreased in dependence of the milling cycles carried out. As the enthalpic relaxation process is an action in which the material gains a higher stability this means that the energy insertion during the milling process enables the polymeric chains to arrange themselves in a more stable conformation. Entrapped drug amounts can be kept isolated. Drug at the particle surface can be further stabilized by smoothened polymeric material which is caused by the forces during the milling process. This softened polymer acts as a coating on the pores of the microparticles as well as drug particles at the particle surface, and thus prevents an immediate drug release here.
Schlagworte:Polymilchsäure ; Polyglykolsäuren ; Blockcopolymere ; Mikrostruktur ; Einfriertemperatur ; Langzeitverhalten ; Blockcopolymere ; Biologisch abbaubarer Kunststoff ; Mikropartikel ; Arzneistoffträger ; Herstellung ; Prozessentwicklung
melt-grinding-technique, microparticle, solvent-free, glass-transition temperature, twin-screw extruder, burst-effect
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