多奈哌齐植入剂的制备及体内外研究  

Preparation and in Vitro and in Vivo Studies of Donepezil Implants

作　　者：颜携国 刘代春 曾哲 YAN Xieguo;LIU Daichun;ZENG Zhe(Drug Research Institute,Shenzhen ScienCare Pharmaceutical Co.,Ltd.,Shenzhen 518118,China)

机构地区：[1]深圳善康医药科技股份有限公司药物研究院,广东深圳518118

出　　处：《山东化工》2024年第23期70-74,共5页Shandong Chemical Industry

摘　　要：目的:研究开发一种基于微球压片结合包衣的多奈哌齐植入(DPZ-IM)新制备技术,并通过体内外评估其作为一种持续释放给药系统的优势,对减少给药频率、降低血药波动以及提高患者依从性具有重要意义。方法:DPZ-IM采用聚乳酸(PLA),通过水-油-水复乳溶剂蒸发技术制备成微球(DPZ-MS),经过压缩成棒状后再用PLA溶液包衣。对体外的表面形态、粒径分布、XRD、载药量、包封率、热分析、溶出度及制剂稳定性等进行考察,并且体内进行药代动力学研究。结果:DPZ-MS的D 50粒径在122.3μm,DPZ-IM的载药量为60.1%(质量分数),包封率为96.6%。DPZ-IM的体外溶出度表明,多奈哌齐在溶出介质中80 d累积释放度达到80.0%以上,比DPZ-MS具备更长效更稳定的释放行为。而体内研究表明,DPZ-IM(25 mg/kg)在大鼠体内持续释放,第10天达到峰浓度,然后缓慢下降,第60天结束。DPZ-IM的缓释时间显著优于DPZ的24 h和DPZ-MS的20 d。结论:DPZ-IM作为一种缓释给药策略,显著提高多奈哌齐的治疗周期,可实现每两月给药一次,而且血药浓度更平稳。Objective:We aimed to develop a new preparation technology for donepezil implants(DPZ-IM)using microsphere tableting combined with coating.In vivo and in vitro evaluations to assess the benefits of sustained release.It is significant to reduce fluctuations in blood drug levels and improve patient compliance.Method:DPZ-IM used polylactic acid(PLA)to prepare microspheres(DPZ-MS)through water-oil-water double emulsion solvent evaporation technology.The microspheres were compressed into rods and coated with 2%PLA solution.This study examined the surface morphology,particle size distribution,X-ray diffraction(XRD)analysis,drug loading,encapsulation efficiency,thermal analysis,dissolution and stability,and in vivo pharmacokinetic studies.Results:The particle size of D 50 of DPZ-MS was 122.3μm,and the loading capacity of DPZ-IM was 60.1%,with an encapsulation rate of 96.6%.The in vitro dissolution of DPZ-IM showed that the cumulative release of donepezil in the dissolution medium reached more than 80.0%in 80 days,and had a longer-lasting and more stable release behavior than that of DPZ-MS.In vivo studies showed that DPZ-IM(25 mg/kg)produced a sustained release process in rats,reaching peak concentrations on the 10th day and maintaining them until day 60,with a significantly better-sustained release time than DPZ at 24 hours and DPZ-MS at 20 days.Conclusion:DPZ-IM,as an extended-release dosing strategy,significantly improves the therapeutic cycle of donepezil,allowing bimonthly dosing and smoother blood levels.

关 键 词：多奈哌齐 微球 植入剂 药代动力学 R语言 

分 类 号：TQ460.6[化学工程—制药化工]