溶出速度正.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,Solid dosage form,solution,血 液,dissolution,Membrane permeability,脂溶性和解离度,For a drug to be absorbed it must be present in the form of an aqueous solution at the site of absorption.,第二章 口服药物吸收,第三节影响药物吸收的物理化学因素,溶出速度（Dissolution rate）,影响药物溶出的因素,溶出面积：S,溶解度：C,s,扩散系数 D 和扩散层厚度 h,Surface Area,Surface area of per gram(or per dose)of a solid drug can be enlarged by reducing the particle size.,Fig1.Relationship between surface area and relative absorption of Griseofulvin,Surface area(log),Relative absorption(%),Fig4.Relationship between the particle size and concentration in blood of spironolactone,400mg tablet,100mg capsule,100mg micronized capsule,Time(hr),Concentration(g/ml),Fig3.Excretion of the metabolite after administration of micronized griseofulvin and its solid dispersions,Time(hr),Excretion of 6-demethyl-griseofulvin(mg),PEG6000 solid dispersions,Micronized griseofulvin,Methods of Particle Size,Reduction,Mortar and pestle,Mechanical grinders,Fluid energy mills,Solid dispersions,减小粒径增加药物吸收,在消化道中吸收受溶出速度支配的药物,不适用于,水溶性或弱碱性药物吸收,在胃液中不稳定的药物,对胃肠道有刺激性的药物,irritating effect on G-I tract,Solubility,Crystal forms,Polymorphism,Amorphous form,Solvates,Salt formation,Q2:which is more bioavailablecrystal form of,chloramphenicol palmitate,?,A mp.91 93,B mp.86 87,Fig4.Concentration of Chloramphenicol in serum after administration of suspension of different crystal forms,（A/B）M：100/0;N：75/25;O：50/50;P：25/75;L：0/100,Time(hr),Serum concentration(g/ml),2,4,6,8,10,12,24,4,8,12,16,20,24,t,C,t,C,p,Fig 5.Dissolution and serum concentration of Penicillin V,K salt:,Ca salt:Free acid:,Bemzatjome salt:,反映药物溶出速度快慢的指标,崩解,指固体制剂在检查时限内全部溶散成碎粒，除不溶性包衣材料或破碎的胶囊壳外，均应通过筛网,药物从固体制剂中溶解释放的前提和先决条件,溶出度,固体制剂中药物在规定的介质中溶出的速度和程度,一定程度上反映药物的吸收情况，可作为固体制剂的内在质量标准,难溶性或溶出慢的药物；药理作用强、安全指数窄的药物,D-diffusion coefficient,S-surface area,C,s,-saturation solubility,C-the concentration of the drug in the bulk solution,h-thickness of the stagnant layer,k-dissolution coefficient,谢谢！再见！,