④t生Physicochemical factors-Dissolution 国生 Effective surface area of the drug Physicochemical factors ·Dissolution ·Particle size Oil/water partition coefficient ·pKa .Disintegration and deaggregation ·Molecular weight Effect of manufacturing processes 国丛生 Physicochemical factors-Dissolution 国话生Physicochemical factors-Kow Saturation Solubility of the Drug ©Oil/Water Partition Coefficients(Kow） ·Salt form of the drug ·pH effect 图KONF Drug concentration in oil phase ·Solvate formation溶剂化物 Drug concentration in water phase ·Polymorphism多晶型 Fick's first law of diffusion: ·Complexation .Solid-solid interaction dQ dt Da 圈生一 Physicochemical factors-Dissolution 圈屹Physicochemical factors-Kow Drug concentration in bulk solution Nernst-Brunner equation It is generally believed that drug molecules must be 4Q-DAC-C) lipophilic to have good absorption because drug molecules must penetrate the lipid bilayer of most ·Sink condition漏悟条件 cellular membranes. ·Assumption:Cb<Cs Compound with extremely high lipophilicity would be unable to enter the aqueous cytosolic domain,and If a drug is absorbed through the GI membrane very slowly,drug concentration in the GIT fluids may build so would be unable to exit from the lipophilic up.This buildup would,by decreasing the gradient. membrane. decrease the dissolution rate. 55 Shanghai Jiao Tong University Physicochemical factors-Dissolution Effective surface area of the drug • Particle size • Disintegration and deaggregation • Effect of manufacturing processes Shanghai Jiao Tong University Physicochemical factors-Dissolution Saturation Solubility of the Drug • Salt form of the drug • pH effect • Solvate formation溶剂化物 • Polymorphism 多晶型 • Complexation • Solid-solid interaction Shanghai Jiao Tong University Physicochemical factors-Dissolution Drug concentration in bulk solution • Nernst-Brunner equation • Sink condition漏槽条件 • Assumption: Cb<<CS • If a drug is absorbed through the GI membrane very slowly, drug concentration in the GIT fluids may build up. This buildup would, by decreasing the gradient, decrease the dissolution rate. Shanghai Jiao Tong University Physicochemical factors • Dissolution • Oil/water partition coefficient • pKa • Molecular weight Shanghai Jiao Tong University Drug concentration in oil phase KO/W= Drug concentration in water phase Physicochemical factors-KO/W Oil/Water Partition Coefficients (KO/W) Fick’s first law of diffusion: Shanghai Jiao Tong University Physicochemical factors-KO/W It is generally believed that drug molecules must be lipophilic to have good absorption because drug molecules must penetrate the lipid bilayer of most cellular membranes. Compound with extremely high lipophilicity would be unable to enter the aqueous cytosolic domain, and so would be unable to exit from the lipophilic membrane