| 18721875 |
Korber M, Bodmeier R: Development of an in situ forming PLGA drug delivery system I. Eur J Pharm Sci. 2008 Nov 15;35(4):283-92. Epub 2008 Jul 31.
Characterization of a non-aqueous protein precipitation.. The incorporation of the model protein hen egg white lysozyme into liquid in situ forming poly (lactide-co-glycolide) (PLGA) implant or microparticle formulations was investigated. Ternary solvent blends of dimethyl sulfoxide (DMSO), ethyl acetate and water were used to adjust the protein solubility in order to facilitate the incorporation of either dispersed or dissolved protein into the polymer solution. Lysozyme formed large gel particles when dispersed directly in the polymer solution. These formulations had a pronounced initial release. Non-aqueous precipitation of lysozyme from solutions in DMSO with ethyl acetate led to a reversible aggregation without loss in biological activity. Lysozyme could be incorporated in a finely dispersed state through an in situ precipitation by non-solvent or polymer addition. Non-aqueous precipitation could thus be utilized to manufacture biodegradable in situ forming drug delivery systems containing homogeneously distributed and bioactive protein. |
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