TY - JOUR A1 - Müller, R.H. A1 - Runge, S. A1 - Ravelli, V. A1 - Mehnert, W. A1 - Thünemann, Andreas A1 - Souto, E.B. T1 - Oral bioavailability of cyclosporine: Solid lipid nanoparticles (SLN®) versus drug nanocrystals N2 - For the development of an optimized oral formulation for cyclosporine A, 2% of this drug has been formulated in solid lipid nanoparticles (SLN™, mean size 157 nm) and as nanocrystals (mean size 962 nm). The encapsulation rate of SLN was found to be 96.1%. Nanocrystals are composed of 100% of drug. For the assessment of the pharmacokinetic parameters the developed formulations have been administered via oral route to three young pigs. Comparison studies with a commercial Sandimmun Neoral/Optoral® used as reference have been performed. The blood profiles observed after oral administration of the commercial microemulsion Sandimmun® revealed a fast absorption of drug leading to the observation of a plasma peak above 1000 ng/ml within the first 2 h. For drug nanocrystals most of the blood concentrations were in the range between 30 and 70 ng/ml over a period of 14 h. These values were very low, showing huge differences between the measuring time points and between the tested animals. On the contrary, administration of cyclosporine-loaded SLN led to a mean plasma profile with almost similarly low variations in comparison to the reference microemulsion, however with no initial blood peak as observed with the Sandimmun Neoral/Optoral®. Comparing the area under the curves (AUC) obtained with the tested animals it could be stated that the SLN™ formulation avoids side effects by lacking blood concentrations higher than 1000 ng/ml. In this study it has been proved that using SLN™ as a drug carrier for oral administration of cyclosporine A a low variation in bioavailability of the drug and simultaneously avoiding the plasma peak typical of the first Sandimmun® formulation can be achieved. KW - Solid lipid nanoparticles KW - SLN KW - Drug nanocrystals KW - Sandimmun Neoral/Optoral KW - Oral administration PY - 2006 DO - https://doi.org/10.1016/j.ijpharm.2006.02.045 SN - 0378-5173 SN - 1873-3476 VL - 317 IS - 1 SP - 82 EP - 89 PB - Elsevier CY - Amsterdam AN - OPUS4-12464 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Müller, R.H. A1 - Runge, S.A. A1 - Ravelli, V. A1 - Thünemann, Andreas A1 - Mehnert, W. A1 - Souto, E.B. T1 - Cyclosporine-loaded solid lipid nanoparticles (SLN): Drug-lipid physicochemical interactions and characterization of drug incorporation N2 - 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 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. KW - Solid lipid nanoparticles KW - Cyclosporine A KW - Characterization KW - Oral bioavailability KW - Lipid polymorphism PY - 2008 DO - https://doi.org/10.1016/j.ejpb.2007.07.006 SN - 0939-6411 SN - 1873-3441 VL - 68 IS - 3 SP - 535 EP - 544 PB - Elsevier CY - Amsterdam AN - OPUS4-17534 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -