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Cyclosporine-loaded solid lipid nanoparticles (SLN): Drug-lipid physicochemical interactions and characterization of drug incorporation

  • Solid lipid nanoparticles (SLN) were produced loaded with cyclosporine A in order to develop an improved oral formulation. In this study, the particles were characterized with regard to the structure of the lipid particle matrix, being a determining factor for mode of drug incorporation and drug release. Differential scanning calorimetry (DSC) and wide-angle X-ray scattering (WAXS) measurements were employed for the analysis of the polymorphic modifications and mode of drug incorporation. Particles were produced using Imwitor®900 as lipid matrix (the suspension consisted of 10% particles, 8% Imwitor®900, 2% cyclosporine A), 2.5% Tagat S, 0.5% sodium cholate and 87% water. DSC and WAXS were used to analyse bulk lipid, bulk drug, drug incorporated in the bulk and unloaded and drug-loaded SLN dispersions. The processing of the bulk lipid into nanoparticles was accompanied by a polymorphic transformation from the ß to the α-modification. After production, the drug-free SLN dispersionsSolid lipid nanoparticles (SLN) were produced loaded with cyclosporine A in order to develop an improved oral formulation. In this study, the particles were characterized with regard to the structure of the lipid particle matrix, being a determining factor for mode of drug incorporation and drug release. Differential scanning calorimetry (DSC) and wide-angle X-ray scattering (WAXS) measurements were employed for the analysis of the polymorphic modifications and mode of drug incorporation. Particles were produced using Imwitor®900 as lipid matrix (the suspension consisted of 10% particles, 8% Imwitor®900, 2% cyclosporine A), 2.5% Tagat S, 0.5% sodium cholate and 87% water. DSC and WAXS were used to analyse bulk lipid, bulk drug, drug incorporated in the bulk and unloaded and drug-loaded SLN dispersions. The processing of the bulk lipid into nanoparticles was accompanied by a polymorphic transformation from the ß to the α-modification. After production, the drug-free SLN dispersions converted back to ß-modification, while the drug-loaded SLN stayed primarily in α-modification. After incorporation of cyclosporine A into SLN, the peptide lost its crystalline character. Based on WAXS data, it could be concluded that cyclosporine is molecularly dispersed in between the fatty acid chains of the liquid-crystalline α-modification fraction of the loaded SLN.zeige mehrzeige weniger

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Metadaten
Autor*innen:R.H. Müller, S.A. Runge, V. Ravelli, Andreas ThünemannORCiD, W. Mehnert, E.B. Souto
Dokumenttyp:Zeitschriftenartikel
Veröffentlichungsform:Verlagsliteratur
Sprache:Englisch
Titel des übergeordneten Werkes (Englisch):European journal of pharmaceutics and biopharmaceutics
Jahr der Erstveröffentlichung:2008
Herausgeber (Institution):Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik
Verlag:Elsevier
Verlagsort:Amsterdam
Jahrgang/Band:68
Ausgabe/Heft:3
Erste Seite:535
Letzte Seite:544
Freie Schlagwörter:Characterization; Cyclosporine A; Lipid polymorphism; Oral bioavailability; Solid lipid nanoparticles
DOI:10.1016/j.ejpb.2007.07.006
ISSN:0939-6411
ISSN:1873-3441
Verfügbarkeit des Dokuments:Physisches Exemplar in der Bibliothek der BAM vorhanden ("Hardcopy Access")
Bibliotheksstandort:Sonderstandort: Publica-Schrank
Datum der Freischaltung:19.02.2016
Referierte Publikation:Ja
Datum der Eintragung als referierte Publikation:05.06.2008
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