From Starch to Starch Microspheres. Formation of an Ordered Structure during Processing

Sammanfattning: Starch microsphere is a dosage form suitable for the encapsulation of protein drugs. The starch microspheres investigated in this thesis are intended for release of the drug in a pre-designed way, or in controlled manner. For this purpose the starch microspheres can be coated by poly(DL-lactide-co-glycolide) (PLG) film, which is a release controlling. The term microsphere quality is complicated and includes parameters ranging from the microscopic appearance (i.e. shape, surface morphology) and physical properties (e.g. crystallinity), to the yield of the microspheres, encapsulation efficiency and release kinetics. The ideal starch particle should be of spherical or close to spherical form, of desired size, with well-defined and sharp particle contours, non-damaged, non-aggregated and non-brittle at handling, since these properties might impact the coating of the particles, as well as administration through the injection and the subsequent release. These ideal particles should be produced with high yield, be able to encapsulate a high level of the protein available and be able to release the protein in the controlled manner. In this thesis it has been shown that the microspheres can be produced of different qualities. The quality has been shown to be influenced by the type of starch, by the type of protein, by the buffer used, by individual incubation times at the two temperatures, 6 ?C and 37 ?C, by the total incubation time, and by relationships between the incubation times at these two temperatures. The process of producing starch microparticles in this thesis was described in terms of starch crystallization and obtained double helical and crystalline order. This ordered structure could be related to efficiency of entrapment of the active substance, its subsequent release and starch degradation rate. Crystallization of starch in the microspheres during the production was compared to crystallization of starch in stored dispersions. It was observed that crystallization of starch during microsphere production proceeded differently from what had been previously reported for stored starch dispersions. In order to investigate the crystallization within microspheres thoroughly this work has been carried out corresponding to a number of variables.