口服固体缓释制剂工艺.pdf

口服固体缓释制剂工艺 李冬 2016/10/26 缓释制剂概述 Why oral modified release?为什么开发控释制剂 Drivers for modified release 研发缓释制剂的驱动力 ? Therapeutic efficacy疗效 ? Optimizing performance优化产品性能 ? Challenging API有挑战性的API ? Reducing side-effects减少副作用 ? Prolonging action延长作用时间 ? Improving patient compliance提升患者的顺应性 ? Minimizing variability最小化差异 ? Life-cycle management产品的生命周期管理 ? Bypassing IP hurdle绕过专利壁垒 2 缓释制剂概述 Types of modified release dosage forms 控释剂型的种类 ? Modified release dosage forms 缓释剂型的定义 与速释制剂的给药途径相同，但以一定的速率或在特定部位释放药物活性成分的制剂。 ? Delayed release dosage forms迟释剂型 The release of the active substance is delayed for a predefined period after administration or application of the dosage form and then releases as a conventional dosage form resulting in a lag time without any change in other pharmacokinetic parameters. ? Sustained release = Extended release = Prolonged release dosage forms 持续释放=扩展释放=延长释放剂型 Dosage forms showing a slower release than that of the conventional release dosage form administered by the same route. ? Multiphasic or programmed release dosage forms 多相或编程释放剂型 e.g. pulsatile release: intended to deliver a burst of drug release at specific time intervals. biphasic release: first phase of drug release = fast release dose fraction, second phase = extended release ? Site-specific release = targeted release dosage forms 靶点释放=目标释放剂型 definitions based on EMA guidelines EMA/CPMP/EWP/280/96 Corr1 and EMA/CHMP/QWP/428693/2013 ?3 缓释制剂概述 哪些种类的API会从缓释制剂开发中收益? e.g. ? APIs with fast elimination ? APIs with small therapeutic window ? APIs that so far have to be dosed frequently, e.g. several times per day ? very hydrophilic and well soluble APIs where the kinetics are to be controlled ? … ? almost every API can potentially benefit, depending on the