新药制剂设计1.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,Five steps,1.the design of dosage form,2.the selection of accessories,3.Preparation technology,4.Package selection,5.quality examination,The four principles,safey,effectiveness,stabilities,controllability,compliance,1.1Physical or chemical property,crystal structure,The distribution of particle size,solubility,melting point,partition coefficient/dissociation degree,acidity and alkalinity/salt formation,stability,logP&logD,1.3 Production feasibility,1.4 Economic cost,2,the selection of accessories,Non toxic and harmless,does not react with the main drug,the physical and chemical properties,with,stability,preservatives,(,benzoic acid,Nipagin Esters,),fille,r(,microcrystalline cellulose,starch,),lubricant,(,talcum powder,),moisturizing agent,(,polyethylene glycol,),tackifier,(,starch,),eg.nasal liposome,a.Phospholipids:Structural features of phospholipids as hydrophilic groups of a phosphate group and a quaternary ammonium salt composition,and consists of two long alkyl lipophilic groups.,Natural lecithin(PC),Synthesis of phospholipids DPPC(DPPE),(DSPC),b.cholesterol,:cregulate the membrane fluidity of liposome,磷脂类：包括天然磷脂和合成磷脂二类。磷脂的结构特点为一个磷酸基和一个季铵盐基组成的亲水性基团，以及由两个较长的烃基组成的亲脂性基团。,天然磷脂以卵磷脂（磷脂酰胆碱，PC）为主，来源于蛋黄和大豆，显中性。,合成磷脂主要有DPPC（二棕榈酰磷脂酰胆碱）、DPPE（二棕榈酰磷脂酰乙醇胺）、DSPC（二硬脂酰磷脂酰胆碱）等，其均属氢化磷脂类，具有性质稳定，抗氧化性强，成品稳定等特点，是国外首选的辅料。,2、胆固醇：胆固醇与磷脂是共同构成细胞膜和脂质体的基础物质。胆固醇具有调节膜流动性的作用，故可称为脂质体“流动性缓冲剂”。,3.Preparation technology,water-in-water emulsion and freeze-drying techniqu,e.,Dehydration and Rehydration(DRV)method.,evaporation-sonication and extrusion.,Thin film hydration,sonication,High pressure homogenization method,double emulsion(wateroilwater)and solvent evaporation method.,Film dispersion method filter and solvent evaporation,5.,Q,uality examination,encapsulation efficiency=(total amount of drugs-amount of drugs in supernatant)/total amount of drugs added initially *100%,core loading=,(total amount of drugs-amount of drugs in supernatant)/total amount of drug loaded dosage*100%,包封率（W 总W 游）/W 总100%,载药量（W 总W 游）/W 混100%W 总为投入总药物量，W 游为未包入脂质体的游离药物,，W 混为脂质体的总量。,5.,Q,uality examination,Subject:surface properties and zeta potential,Method:DLS(dynamic light scattering),The method of separation of free drug:dialysis/Sephadex G-50/centrifugation/protamine aggregation,Phase transition temperature,1.1Physical or chemical property,crystal structure,The distribution of particle size,solubility,melting point,partition coefficient/dissociation degree,acidity and alkalinity/salt formation,stability,logP&logD,