Biocompatible riboflavin laurate long-acting injectable nanosuspensions allowing sterile filtration.

The aim of this research was to prepare biocompatible riboflavin laurate (RFL) long-acting injectable nanosuspensions for intramuscular injection with a small particle size allowing sterile filtration. RFL nanosuspensions were manufactured by a precipitation-combined high-pressure homogenization method. Three kinds of mixed stabilizers-d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a primary stabilizer, and egg lecithin (PL-100M), Kollidon VA64, Kollidon S-630 as a secondary stabilizer, were separately applied to avoid further aggregation. In the three optimized formulations, the mean particle size of the RFL nanosuspensions was about 170 nm allowing sterilization by filtration. Results from transmission electron microscopy, differential scanning calorimeter, powder X-ray diffraction and Fourier transform infrared reflectance spectroscopy revealed that RFL existed as rod-like crystals. However, a few nano-spheres under 100 nm were found only when PL-100 was used as a secondary stabilizer, possibly due to TPGS and PL-100, which inserted into RFL during the process of crystallization and homogenization. In irritation testing, RFL long-acting injection (LAI) stabilized by TPGS and PL-100 led to mild paw-licking responses and a slight inflammatory reaction, which returned to normal by 14 d after administration. The endogenous PL-100 and nano-spheres with a small size may have contributed to the excellent biocompatibility. As a result, TPGS and PL-100 were selected as blended stabilizers to prepare the irritation-free RFL-LAI that could be sterilized by passage through a 0.22 µm millipore membrane filter.

Increased absorption of mangiferin in the gastrointestinal tract and its mechanism of action by absorption enhancers in rats.

The therapeutic efficiency of mangiferin is restricted by its low intestinal permeability. In order to improve the oral absorption of mangiferin, potential of enhancers, including TPGS, sodium deoxycholate and Carbopol 974P, were investigated in a series of in vivo experiments. After administration of mangiferin at a dose of 30 mg/kg combining with sodium deoxycholate, the bioavailability of mangiferin increased four-fold, and this may be due to sodium deoxycholate weakening the compactness between lecithin molecules and increased the paracellular permeability. When Carbopol 974P (100 mg/kg) was combined with mangiferin, the oral bioavailability of it increased seven-fold compared with the control group, and this may be related to the mucoadhesive properties of Carbopol 974P and paracellular drug permeation. However, following coadministration of TPGS (50 mg/kg), the oral absorption of mangiferin increased slightly compared with that of the control group (p > 0.05). The increased oral absorption by the three coexcipients was in the order of Carbopol 974P > sodium deoxycholate > TPGS. The absolute bioavailability of mangiferin in the three different doses following oral administration were evaluated based on the AUC(0-t) of the intravenous dose and there was no increase from low doses to high doses (25 mg/kg to 100 mg/kg). The above results show that the low absorption of mangiferin was due to presence of a narrow absorption window, which may also exist in these compounds, which have structures similar to mangiferin including three fused aromatic rings with polyphenolic hydroxyl groups. Bioadhesion polymers are effective enhancers of the absorption of mangiferin in the gastrointestinal tract.