Study On Pellets Of XL-4-26 Solid Dispersions And XL-4-26 Solid Dispersions

XL-4-26, an anti-aids drug, was used as model drug to do research of solid dispersions (SD) and pellets. The properties of insolubility and poor absorption of this drug made it low bioavailability in vivo. In our study XL-4-26 was made into SD, which was formed to increase the dissolution and the bioavailability.According to the literature, UV spectrophotometry was developed for in vitro assay of content and drug dissolution. Recovery and precision were investigated.High-performance liquid chromatography (HPLC) was applied in the determination of solubility in different media and content of related substance in pellets.The solid dispersions were prepared by the solvent evaporation method and the solvent-melting method with polyvinylpyrrolidone (PVP-k30) and polyethylene glycol (PEG-6000) as carriers in different ratios, respectively. The influences of different kinds of carriers and agent-carrier proportion on the dissolution of XL-4-26 were examined. Finally, it showed that PVP-k30 was the best carrier. The DSC curves proved that after forming the solid dispersion with PVP-k30, the thermal characteristic of XL-4-26 was sheltered. That meant the solid dispersion of XL-4-26 was in an amorphous form.The in vivo dissolution behavior of XL-4-26 and XL-4-26 SD were detected in rats after oral administration (p.o.), compared with intravenous injection (i.v.) of XL-4-26 solution. After of single oral administration of XL-4-26 and XL-4-26 SD, AUC of the two groups were 32375.3±1009.7 and 142804.188±16239.7 (μg/L*min) respectively; Cmax were 134.95±57.35 and 678.56±100.15 (μg/L) respectively; The relative bioavailability of XL-4-26 SD(1:1) was 441.09%. XL-4-26/PVP-k30(1:1) was selected as the best formulation to the pellets test. The results showed that XL-4-26 SD can better the bioavailability of XL-4-26.In addition, basing on the results of single-factor tests, orthogonal design test was carried out to optimize the formulation and preparation process. The pellets achieved using the optimized formulation and preparation process had dissolution of higher than 70% at 45min.Stability studies of XL-4-26 pellets showed that light, temperature and air had little influence on the content and dissolution behavior of drug, but the increasing weight 10.83%, after it was deposited in condition of high humidity after 10 days.