圈上攻达线 Physicochemical factors-Dissolution 圈生一 Physicochemical factors-Dissolution Drug concentration in bulk solution Nernst-Brunner equation Nernst-Brunner equation 4Q=DA C-Cx) 4Q-DAC-C2 故 h .Effective surface area of the drug ·Sink condition漏槽条件 ·Assumption:Cb<<Cs Saturation solubility of the drug Drug concentration in bulk solution If a drug is absorbed through the GI membrane very slowly,drug concentration in the GIT fluids may build Diffursion coefficient up.This buildup would,by decreasing the gradient, decrease the dissolution rate. Thickness of the stationary diffusion layer 圈线_Physicochemical factors--Dissolution 国线一 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 Physicochemical factors-Dissolution 圈屹Physicochemical factors-Kow Saturation Solubility of the Drug Oil/Water Partition Coefficients(Ko) ·Salt form of the drug Drug concentration in oil phase ·pH effect ©KowF ·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 d dt 55 Shanghai Jiao Tong University Nernst-Brunner equation • Effective surface area of the drug • Saturation solubility of the drug • Drug concentration in bulk solution • Diffusion coefficient • Thickness of the stationary diffusion layer Physicochemical factors-Dissolution 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: