第十章：栓剂
栓剂系指药物与适宜基质制成的具有一定形状供人体腔道给药的固体制剂。栓剂在常温下为固体，塞入腔道后，在体温下能迅速软化、熔融或溶解于分泌物，逐渐释放药物产生局部或全身作用
栓剂给药：1.直肠静脉－门静脉－肝脏－血液循环 2.直肠中下静脉－髂内静脉－
下腔静脉－血液循环 3. 直肠淋巴系统（不通过肝脏）4. 阴道静脉－下腔静脉－血液循环
快速释放药物：油脂性基质 释放区域：1.从肛门相距2厘米：50－75％药物直接吸收道体循环 2.相距6厘米：主要吸收到肝门静脉系统
栓剂的基质因素：1.油脂性基质 软化熔融释放药物 2.水溶性基质 溶解释放药物
油脂性基质：可可豆脂 混合脂肪酸甘油酯 椰油酯 棕榈酸酯 硬脂酸丙二醇酯
水溶性基质：甘油明胶 PEG聚氧乙烯 泊洛沙姆
甘油明胶（gelatin glycerin）：1.由明胶（20％）在甘油（70％）中溶解，在药物治疗中加溶液或混悬液（10％） 2.常用于阴道栓剂的制备，延长局部作用 3.明胶的吸湿性:在没有水分动态的环境下保存 放入前要沾水 防腐剂：尼泊金
栓剂模型的润滑剂：液体石蜡或植物油（水溶性基质） 软肥皂和甘油的醇溶液（油脂性基质）
置换价：药物的重量与同体积栓剂基质的重量之比
与生物利用度关系最密切：熔变时限：油脂性基质：30min内全融化，软化或无硬心 水溶性基质：60min内全部溶解
第十一章：软膏剂（misolid dosage forms）
Definition：include ointments, creams, pastes and gels)
consist of drug(s), ba and other additive(s) for topical application(skin, eye, nasal cavity, vagina or rectum)
Function: 1. physical effects (nonmedicated) as emollients, protectants or lubricants
2. Topical therapeutic effects (The majority of ointments)
3. Systemic effects (percutaneous absorption)
Ointment bas: hydrocarbon bas, absorption bas, water-removable bas, water-soluble bas, fatty or oleaginous bas, emulsion bas (w/o, o/w), water-soluble bas
Primary features of hydrocarbon bas (oleaginous bas)
1.Water-free 2. Emollient effect 3. Retention on the skin for prolonged periods 4.prevention of escape of moisture from the skin to the atmosphere 5.difficult in washing off
代表性材料：Valine, white petrolatum, paraffin and liquid paraffin, wool fat, beeswax, silicones
Valine: 1. A mixture of misolid hydrocarbons obtained from petroleum
2.An unctuous mass, varying in color from yellowish to light amber
3.Melts at temperatures between 38 and 60°C
4.Good spreading nature and thickness
5.Bad water absorption
6.Is ud in combination with wool fat, cholesterol, long-chain fatty alcohol to improve its water absorption
7.Is ud in combination with surfactants to improve its water absorption
Dimethicone (silicones): often be applied in protection-aimed ointments with an amount up to 30%
Absorption bas(代表性材料): cholesterol, stearyl alcohol, white wax, lanolin
Features of water-removable bas: 1. o/w emulsions 2. Are capable of being washed off with water 3. Have the ability to absorb rious discharges 4. Also have emollient effect
Emulsion bas: 1.have certain affinity for both water and oil 2. Have preferable relea of drug from bas 3. Can better deliver drug through skin and mucous membranes 4. Can absorb the diffusate of wounded areas 5. Are liable to spread and washout
O/W: Becau the external pha of the emulsion is aqueous, 防腐剂 agents and 保湿剂 are often added.
Features of water-soluble bas: 1. Contain only water soluble components 2. Are difficult of incorporation of aqueous solutions becau they soften greatly with the addition of water
Water-soluble bas(代表性材料)：PEG, CMC-Na
Emulsion process: 1. The oil pha ingredient are combined and heated between 70 and 75°C 2. The aqueous pha ingredients are heated together to slightly above 75°C
Ophthalmic ointments: have a lasting curative effect than eye drops can lighten attrition between eyelid and eyeball are convenient to carry
Ba: Valine: liquid paraffin: wool fat=8:1:1
Gels: definition: are misolid systems consisting of drug(s) water and gelling agent(s) rendering the aqueous liquid vehicle jelly-like
Type: single-pha gels: macromolecule; no pha boundaries
Two-pha gels: floccules of small particles
Ba: cellulo derivatives( CMC-Na, HPMC, MC), glycerogelatin, carbopol
第十五章：缓释、控释和迟释制剂
缓释制剂：在规定释放介质中，按要求缓慢地一级速率释放药物，给药频率比普通制剂减小一半或给药总剂量比普通制剂有所减少，且能增加患者顺应性的制剂。
特点：1。减少给药次数 2。使血药浓度平稳 3。可减少用药的总剂量 4。剂量调节灵活性降低 5。设备和工艺费用较常规制剂昂贵
不适合药物：剂量很大（大于1g） 半衰期很短（小于1h）或很长（大于24h）
不能在小肠下端有效吸收
口服后各种骨架片形态变化的差异（见PPT）
渗透压原理：利用渗透压原理制成的控释制剂，能均匀恒速地释放药物，比骨架型缓释制剂更为优越 水不溶透衣膜：醋酸纤维素;EC;EVA 可均匀恒速释药，且释药速率不受肠胃液的pH、搅拌速度和胃肠蠕动等影响
释药原理和方法：离子交换作用：酸性药物－阴离子交换树脂 碱性药物－阳离子交换树脂 载药量小 混悬液选用何种水 可微囊化（包衣）
亲水凝胶骨架材料：天然胶 如果胶、海藻酸盐、琼脂、西黄芪胶
纤维素衍生物 如MC,HEC,HPC,HPMC,CMC-Na
非纤维素多糖：葡聚糖 甲壳素 壳聚糖
乙烯基聚合物或丙烯酸树脂；PVA 聚羧乙烯
生物溶蚀性骨架材料：蜂蜡、硬脂酸、氢化植物油、单硬脂酸甘油酯、硬脂醇
不溶性骨架材料：EC、聚乙烯、聚丙烯、聚硅氧烷和PVC
天然高分子囊材：海藻酸盐：钠盐＋CaCl2=不溶性钙盐（可用于其固化成囊）
合成高分子囊材：生物可降解：聚碳酯、聚氨基酸、PLA、PLGA、PLA－PEG、ε-己内酯与丙交酯嵌段共聚物
微囊的制备：单凝聚法；凝聚剂：强亲水性电解质：硫酸钠
强亲水性非电解质：乙醇
交联固化剂：明胶－甲醛（pH8－9）；戊二醛（中性介质） 囊材组合：明胶与阿拉伯胶（或CMC、CAP等多糖）
