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Abstract: Sorafenib is slightly absorbed in the gastrointestinal tract due to its poor solubility in water. To improve its absorption, a novel nanoparticulate formulation-nanomatrix was used in the study. The nanomatrix was a system prepared from a porous material Sylysia® 350 and a pH sensitive polymer Eudragit®. The formulations were optimized by orthogonal design (L9(34)) and their bioavailability were evaluated in rat, comparing to pH-sensitive Eudragit nanoparticles and suspension of sorafenib. In the formulations, the ratio of sorafenib to Eudragit® S100 was found to be more important determinant of the sorafenib bioavailability than the ratio of sorafenib to Sylysia® 350. As for the bioavailability, the AUC0–36h of sorafenib nanomatrix was 13–33 times to that of sorafenib suspension, but only 16.8% to 40.8% that of Eudragit® S100 nanoparticles. This may be resulted from the different drug dispersion degree, release character and bioadhension activity. However, because all the materials used in the nanomatrix formulation are commonly adjuvant, safe, easy to get and cheap, above all, the nanomatrix formulation can solve the stability and scaling up problems in the nanoparticles, it had potential to develop into a product in the future. [Copyright &y& Elsevier]

Abstract: The present study was geared at the long-term stability and the changes in oral bioavailability of CyA Eudragit® S100 nanoparticles stabilized by suspending agents. CyA Eudragit® S100 nanoparticle colloids were prepared by quasi-emulsion solvent diffusion technique and they were mixed with Xanthan gum to obtain suspended nanoparticle colloids. The suspended nanoparticle colloids were preserved at different temperatures for different period of time, as long as 18 months. During the storage period, the CyA concentration, particle size, pH and viscosity were determined. The results indicated that CyA concentration, particle size and viscosity of the colloids had no obvious change. However, the pH increased slightly from 5.5 to about 6.4. The results of bioavailability and pharmacokinetic study revealed that all formulations of nanoparticles showed higher C max and higher AUC0–24 values than that of reference (Neoral®). The relative bioavailability of S-CyA-S100 NP initial compared with Neoral® was 162.8%. The C max and AUC0–24 values of nanoparticle formulations at 12 and 18 months were both lower than that of the initial. The bioequivalency was suggested between the tested nanoparticle formulations at the initial and 12 months. It was deduced by surface analysis, TEM observation, in vitro release as well as the characteristics of Eudragit® S100 that the decrease in bioavailability might be due to the pH change of the nanoparticle colloid. [Copyright &y& Elsevier]

The pH-sensitive cyclosporine A (CyA) nanoparticles were prepared by the solvent displacement method with enteric dissolved polymer of hydroxypropyl methylcellulose phthalate (HPMCP; including HP50 and HP55). The CyA nanoparticles were analyzed by HPLC for yield and encapsulation efficiency, dynamic light scattering for particle size and transmission electron microscopy (TEM) for morphology. The bioavailability of CyA-HP50 and CyA-HP55 nanoparticle colloids were evaluated in rats, compared with the current available CyA microemulsion (Neoral®). The bioavailability of CyA-HP55 nanoparticle colloids with various suspending agents was also investigated. The results obtained demonstrated that the pH-sensitive CyA nanoparticles with a particle size of 50–60 nm and encapsulation efficiency over 95% could be reproducibly prepared. The bioavailability of CyA-HP50 and CyA-HP55 nanoparticle colloids calculated by the AUC0–72 were 82.3% and 119.6%, similar to the reference of Neoral, while the bioavailability of CyA-HP55 nanoparticle colloids was found to be higher than that of CyA-HP50 nanoparticle colloids. The increase of mean residence time (MRT) and the decrease of elimination constant of the central compartment (K10) for both CyA-HP50 and CyA-HP55 nanoparticle colloids compared with the reference indicated significant sustained release of CyA from the nanoparticles. The effects of the suspending agents on the bioavailability of CyA-HP55 nanoparticles were observed, and the bioavailability decreased as the concentration of suspending agents or the viscosity of the nanoparticle colloids increased. [Copyright &y& Elsevier]