| Paliperidone is a class of second-generation atypical antipsychotic agents, and polyethylene glyol is a kind of water soluble and nontoxic polymer, we modified the structure of paliperidone and then conjugated it with PEG by the method of "grafting to", the ultra-long-lasting sustained release microspheres were prepared to reduce times of administration and the frequency of the adverse drug reaction occurred.High Performance Liquid Chromatography (HPLC) was established to measure the content of paliperidone.We modified the structure of paliperidone by esterification and acylation and then different molecular weight grafted polymers were obtained by grafing polyethylene glyol onto acyl chloride functionalized paliperidone, and then characterize them. The paliperidone microspheres were prepared by a solvent evaporation method, and the effects of different variables on microspheres particle size were studied.Response surface methodology was adapted to optimize the preparation technology of paliperidone microspheres, using microspheres particle size as evaluation, the effects of the concentration of PEG6000-g-PP, the volume ratio of the continuous phase to the dispersed phase, and the emulsifying speed on microspheres particle size were studied. The best process conditions:the concentration of PEG6000-g-PP was 10 mg/mL, the volume ratio of the continuous phase to the dispersed phase was 11.03, the emulsifying speed was 990.84 rpm. The microspheres under the best process conditions had uniform particle size, the average particle size of microspheres was 5.672 μm, and the content of paliperidone was 7.79%.In this paper, paliperidone microspheres were utilized to investigate the pharmacokinetic studies in vivo in mice, oil soluble suspension agent was employed to obtain microsphere suspension and subcutaneous injection drug administration, the results demonstrated that the plasma concentration of paliperidone microspheres was steady, the duration can reach more than 28 days. |
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