图生 国i生_Ea-release products Design of Sustained-release Systems In vitro-Dissolution test Excipients for sustained release ·Apparatus Matrix material ·Media -Hydrogel .Requirement of drug release -Non-erodible First time point ensures against dose dumping(0.5~2h) -Bioerodible Final time point demonstrates complete release (>75%) Intermediate time points prove control of the ·Coating material release(50%) -Insoluble coating material Dynamics of drug release -Enteric coating material ·Thickener Evaluation of sustained-release products Evaluation of sustained-release products In vivo-Bioavailability In vitro-in vivo correlation ·Volunteers A predictive mathematical model describing Reference formulation the relationship between an in vitro property ·Analysis methods ·Single dose (usually the extent or rate of drug release), ·Multidose and a relevant in vivo response(e.g,plasma ·Statistic analysis concentration or amount of drug absorbed) 国丝生 Learning objectives Learning objectives Understand the mechanisms of different types of Understand factors influencing oral sustained-release dosage form design sustained release systems .Physicochemical factors Dissolution-controlled mechanism ·Dose size Diffusion-controlled mechanism pKa,lonization and aqueous solubility Partition coefficient Bioerodible-controlled mechanism ·Stability .Osmotically-controlled mechanism ·Biological factors ·Half-life lon-Exchange mechanism .Absorption ·Metabolism 66 Shanghai Jiao Tong University Design of Sustained-release Systems • Excipients for sustained release • Matrix material – Hydrogel – Non-erodible – Bioerodible • Coating material – Insoluble coating material – Enteric coating material • Thickener Shanghai Jiao Tong University Evaluation of sustained-release products In vitro-Dissolution test • Apparatus • Media • Requirement of drug release • First time point ensures against dose dumping( 0.5~2h) • Final time point demonstrates complete release ( ＞ 75%) • Intermediate time points prove control of the release( 50%). • Dynamics of drug release Shanghai Jiao Tong University Evaluation of sustained-release products In vivo-Bioavailability • Volunteers • Reference formulation • Analysis methods • Single dose • Multidose • Statistic analysis Shanghai Jiao Tong University Evaluation of sustained-release products In vitro-in vivo correlation • A predictive mathematical model describing the relationship between an in vitro property (usually the extent or rate of drug release), and a relevant in vivo response (e.g., plasma concentration or amount of drug absorbed). Shanghai Jiao Tong University Learning objectives Understand the mechanisms of different types of sustained release systems • Dissolution-controlled mechanism • Diffusion-controlled mechanism • Bioerodible-controlled mechanism • Osmotically-controlled mechanism • Ion-Exchange mechanism Shanghai Jiao Tong University Learning objectives Understand factors influencing oral sustained-release dosage form design • Physicochemical factors • Dose size • pKa, Ionization and aqueous solubility • Partition coefficient • Stability • Biological factors • Half-life • Absorption • Metabolism