Preparation and in vitro/in vivo evaluation of risperidone elementary osmotic pump (RIS-EOP) formulations were investigated. A method for the preparation of RIS-EOP tablets was developed by modulating RIS solubility with citric acid. The influence of osmotic agents and the compositions of semipermeable membrane on drug release profiles was evaluated. The formulation of RIS-EOP was optimized by orthogonal design. The in vitro release profile of the optimum formulation achieved to deliver RIS at an approximate zero-order up to 12 h. The pharmacokinetic profiles of RIS-EOP were evaluated compared with immediate release tablets in beagle dogs. The mean tmax and mean residence time of RIS-EOP for RIS and its active metabolite, 9-hydroxyrisperidone, were remarkably longer, compared with immediate release tablets. These results corroborated prolonged release of RIS from EOP formulations. Moreover, drug plasma levels with lower fluctuations could be achieved with RIS-EOP tablets. These results suggested that increasing drug solubility by adding or reacting with alkali/acid might be used for the preparation of EOP tablets of certain poorly water-soluble drugs.

School of Pharmacy, Zhejiang University, Hangzhou, P.R. China AbstractAn economical, convenient portable drug delivery system combining osmotic pump with subcutaneous infusion was developed, which was composed of three primary components: water chamber, osmotic pump chamber and support base. Ceftriaxone sodium (CRO) was selected as the model drug and osmotic pump tablets were prepared. The influence of osmotic agents on drug release profiles was evaluated. As the adjustment made by the osmotic agents was limited, the compositions of semipermeable membrane were investigated to determine significant associations of factors based on orthogonal design. The in vitro release profiles of the optimum formulation achieved to the predetermined value (15 AE 3 min for the initial release time T i and 5.75 AE 0.25 h for the extent release time T e ). The pharmacokinetic profiles of this drug delivery system were evaluated in Beagle dogs. In vivo results demonstrated that the osmotic pump subcutaneous infusion administration was equivalent to intravenous injection administration in terms of bioavailability. Moreover, constant drug plasma levels with minimized fluctuations could be achieved with this osmotic pump subcutaneous infusion system, compared with intravenous injection.

The low-density lipoprotein receptor-related protein (LRP) was highly expressed in blood brain barrier and glioma cells. Angiopep-2 was a new and effective ligand of LRP. Herein, we present a novel brain targeting delivery system: doxorubicin (DOX) loaded angiopep-2 modified liposome (AL). The particle size of AL was 102 nm and the zeta potential was -9.8 mV, which was stable and suitable for brain targeting delivery. In the anti glioma study, AL group had the smallest average tumor volume, the strongest tumor apoptosis, gain more weight after treatment and longer median survival time than that of other groups. This proved that Angiopep-2 modified doxorubicin liposomes had certain glioma targeting therapeutic effects and lower toxicity.