嘉法狮用于直肠阴道给药的脂质辅料.pdf

Lipid excipients for rectal/vaginal drug delivery 用于直肠/ 阴道给药的脂质辅料 Training for Standard Pharma. Context 背景 o Suppositories are the most effective medication 栓剂是最有效的药物 o By-pass the gastro-intestinal path 绕过胃肠道路径 o Protection from drug degradation due to: 防止药物由于以下因素降解  Enzymatic degradation 酶促降解  Bile salt effect 胆盐效应  pH effect pH影响 o Prevent gastric irritation associated with certain drugs 防止某些药物的胃刺激性 o Avoid hepatic first pass elimination of high clearance drugs 避免药物的肝首过效应 o Generally reach 50 % to 70 % of bioavailability 通常生物利用度达到50%-70% o Immediate absorption: Rapidity of action立即吸收：快速起效 o Convenient for elderly, children and disabled便于老人 ，孩子和残疾人 使用 Mechanisms of absorption 吸收机理 o ADMINISTRATION 给药方式  Suppository in the rectal ampulla 栓剂直肠给药 o RELEASE DRUG 药物释放  Suppository melts and drug is released in the rectum 栓剂融化 ，药物在直肠中释放 o ABSORPTION 吸收  Direct pathway means direct absorption into blood system by inferior and middle haemorrhoidal veins直接途径是通过下 和中直肠静脉直接吸收入血  Indirect pathway means absorption through the liver by superior haemorrhoidal veins 间接途径是通过上直肠静脉通过 肝脏吸收 Main characteristics主要特性 o Non toxic, non irritant, good tolerance 无毒、无刺激性、 良好的耐受性 o Compatible with drugs (chemically inert)和药物相容 （化学惰性） o Good physical stability (hardness and aspect) 好的物理稳定性 （硬度和外观） o Rapid and complete release of active :活性物快速完全释放：  By melting : suppository melts at body temperature 通过融化 ：体温条件下栓剂融化  By diffusion : diffusion of the active from the suppository to the rectal liquid 通过扩散 ：活性物从栓剂中扩散到直肠 液体中 (dependant on the partition coefficient of the active between excipient and rectal fluids) （取决于活性物在辅料和肠液中的分配系数） SUPPOCIRE® Family SUPPOCIRE® 系列