<p>The purpose of this thesis was to develop methods suitable for the incorporation of drug substancessuch as proteins into microparticles intended for controlled release. In particular a novel techniquefor the preparation of microparticles using supercritical fluids was investigated.</p><p>Supercritical fluids offer a considerable promise as extraction media for the formation ofmicroparticles of drugs and pharmaceutical excipients. There are two main reasons for using this technique. Firstly, the selective solvating power of supercritical fluids makes it possible to separatea particular component from a multi-component mixture. Secondly, the favourable mass transfer properties and high solubility of solvent in supercritical fluid make the formation of the microparticles rapid and efficient. </p><p>The Solution Enhanced Dispersion by Supercritical fluids process (SEDS) was used for the production of microparticles from several different biodegradable polymers. Briefly, particles were formed by the extraction of solvent from a solution which was sprayed into a supercritical fluid. </p><p>The use of a combination of supercritical N<sub>2</sub> and CO<sub>2</sub> in the SEDS process, improved the dispersion of polymer solutions, as compared with CO<sub>2</sub> alone. This resulted in reduction of the particle size of discrete microparticles produced from amorphous biodegradable polymers. Proteins (lysozyme and urease) were successfully incorporated into the poly(d,l-lactide-co-glycolide): copolymer composition 50:50 (DL-PLG) microparticles. The particles showed high entrapment efficiencies and the incorporated proteins retained a high degree of biological activity. Compared with conventional technologies for the preparation of such drug delivery systems, e.g. solvent-evaporation emulsion techniques, this new technique is environmentally superior, and suitable for up-scaling. Moreover the higher degree of control as indicated by the high reproducibility, makes validation of the process feasible. In conclusion, the SEDS process is an attractive way of incorporating proteins and peptides into biodegradable microparticles for controlled release.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-1072 |
| Date | January 2000 |
| Creators | Ghaderi, Raouf |
| Publisher | Uppsala University, Department of Pharmacy, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, 0282-7484 ; 234 |
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