缓控释给药系统.ppt

Controlled & Sustained-Release Drug Delivery Systems Pharmaceutics Department China Pharmaceutical University By JianPing Zhou Learning Objectives To master the principle of drug release from DDS To master usual methods to achieve controlled release and their formula design To understand the evaluation of the in-vitro & in-vivo of DDS Outline DDS development Introduction to DDS basic concept, classification, advantage Mechanism 5 types Formula design Common principle influencing factors formula design examples Chapter 1 History of DDS Development Nimodipine、Nifedipine、Nitrendipine、Felodipine; Diclofenac、Naproxen、Tramadol、Morphine; Nitroglycerol、Clonidine、Isosorbide Mononitrate; Ticlopidine Hydrochloridc、Aspirin; Acopolamine (patch)、Norgestrel (implants) Chapter 2 Basic Concept 1、Definition Sustained-release preparation 缓释制剂——较长时间内持续释药 sustained-release ~, extended-release ~, prolonged action ~, repeat-action ~, retarded preparations Controlled-release preparation 控释制剂——以恒定速度药（狭义）。 广义：速度、时间、方向（部位） Controlled Release vs. Sustained Release Sustained release 种类、品种多（约80%） 处方工艺简单 易于工业化大生产 Controlled release 种类、品种较少 处方工艺较复杂 质量标准要求高 Chapter 2 Basic Concept 2、Classification Types of Drug Delivery Systems 1）骨架型（ Matrix）：Hydro gels、Wax、Insoluble matrixes etc. 释药过程flash 2）膜控型（Membrane） ：macro-porous 、micro-porous 、semi-permeable membrane etc. 基本结构picture 3）其它（Others）：Osmotic pumps、Implanted 、 Impulsive preparations、 Transdermal therapeutic system（TTS）、Self-regulated DDS etc. 膜控型微丸基本结构 骨架型片剂释药示意图 Chapter 2 Basic Concept 3、Characteristics Theory of DDS Characteristics 1）Safe：血浓平稳，避免峰谷现象，降低毒副作用； 2）Effect：降低胃肠道刺激，提高生物利用度，减少给药总剂量； 3）Convenience：延长给药间隔，减少服药频率，提高服药依从性（Compliance）。 Quality control：成本较高，制造过程复杂，大生产易出现质量问题（特别是膜控型）。 Chapter 3  Mechanism 5 Types of System Rate-controlled mechanism 1、 Dissolution Controlled Noyes－Whitney Equation ? Developed by Noyes Whitney in 1897 ? ? If c << cs (i.e.,sink conditions) →Methods to get extendin